Em artrópodes o sistema imune inato contribui para a adaptação de animais como os escorpiões à diferentes ambientes. Esse sistema é composto por mecanismos capazes de agir contra injúrias e a ação de microrganismos e entre esses mecanismos estão os peptídeos antimicrobianos (PAMs). O objetivo deste trabalho foi identificar PAMs presentes na hemolinfa de Tityus serrulatus. Para isso sua hemolinfa foi extraída e separados os hemócitos e plasma, em seguida fracionamos em 3 concentrações de acetonitrila em TFA 0,05% (05, 40 e 80%). Estas frações foram submetidas a uma cromatografia liquida de alta eficiência (CLAE) e os picos foram avaliados quanto a sua ação antimicrobiana e hemolítica. Foram identificadas 16 frações que apresentam atividade antimicrobiana. Uma das frações com atividade antimicrobiana, presente nos hemócitos apresentou similaridade com defensina descrita em carrapatos da espécie Ixodes scapularis. Essa fração possui aproximadamente 3486 Da, não apresenta atividade hemolítica e foi denominada como Serrulina. / In arthropods, its innate immune system contributes to the adaptation of animals like scorpions to different environments. This system consists of mechanisms that act avoiding injuries and against the action of microorganisms, among these mechanisms are antimicrobial peptides (AMPs). The aim of this study was to identify AMPs, present in the hemolymph of Tityus serrulatus. The hemolymph was extracted and then we separated hemocyte and plasma. The samples were fractionated in different concentrations of acetonitrile in TFA 0.05% (05, 40 and 80%). These fractions were subjected to high-performance liquid chromatography (HPLC) and the peaks obtained were evaluated for its antimicrobial and hemolytic action. We found sixteen fractions with antimicrobial activity. One of the fractions with antimicrobial activity, present in hemocytes, is similar with a defensin described in ticks, Ixodes scapularis. This fraction has about 3486 Da, has no hemolytic activity and was named as Serrulina.

A malária está entre as doenças mais prevalentes no mundo, acometendo aproximadamente 500 milhões de indivíduos por ano. Sabe-se que a resposta pró-inflamatória proporciona o controle da parasitemia, mas também desencadeia as manifestações clínicas que estão diretamente relacionadas aos casos fatais da doença. A utilização de modelos experimentais contribui para o conhecimento dos mecanismos intrínsecos relacionados à imunidade do hospedeiro. As análises em camundongos infectados com 106 eritrócitos parasitados pelo Plasmodium chabaudi AS mostram que, na fase aguda da malária, ocorre intensa proliferação com parasitemia detectável no dia 4 pós-infecção (p.i.), sendo o pico atingido no dia 7 p.i. e o declínio até o dia 10 p.i .. Acompanhando a cinética do parasita, observa-se o aumento no número de esplenócitos totais. A ativação do sistema imune caracterizasse pelo perfil de resposta Th1, com expansão da população de linfócitos T CD4+ convencionais e linfócitos T CD4+ Foxp3+ reguladores (Treg) e produção predominante de IFN-g. Nesse estudo, avaliamos em camundongos infectados com P. chabaudi AS: 1) O perfil de expressão das moléculas com papel fundamental na resposta imune nas células T CD4+ convencionais e Treg; 2) Os efeitos decorrentes da inibição in vitro das moléculas ICOS e OX40 presentes em ambas as populações celulares na resposta proliferativa a eritrócitos parasitados; 3) A atividade supressora das células Treg, sobre as células T CD4+ convencionais. Os resultados mostram que a partir do dia 4 p.i. ocorreu aumento na porcentagem de células T CD4+ convencionais e Treg, que expressavam as moléculas estimuladoras GITR, OX40 e ICOS. Observamos também que houve correlação entre a maior expressão da molécula CD25 com o aumento das outras moléculas ativadoras presentes nas células T CD4+ convencionais, o mesmo não sendo tão acentuado nas células Treg . Ao inibirmos a ação das moléculas ICOS e OX40, observamos que a inibição de ICOS interferiu de forma mais intensa na proliferação da população de células Treg , enquanto a inibição da molécula OX40 reduziu drasticamente a proliferação das células T CD4+ convencionais e Treg . Os ensaios de supressão indicaram que as células Treg ICOS+ são mais eficientes para controlar a proliferação das células T CD4+ convencionais. Além disso, observamos que, no baço dos camundongos infectados pelo P. chabaudi, ocorreu aumento na porcentagem de células T CD4+ convencionais que expressavam PD-1 e PD-L 1. No entanto, nas células Treg, detectamos diminuição na expressão de PD-1 e aumento de PD-L 1, fornecendo indícios sobre o mecanismo que pode estar envolvido no controle do número de células na fase aguda da infecção. Observamos ainda que, durante a expansão das células T CD4+, não houve modificações na porcentagem de células expressando a molécula CTLA-4 ou no nível de expressão desta molécula nos diferentes dias de infecção. Considerando os dados em conjunto, podemos concluir que a modulação da resposta imune à malária causada pelo P. chabaudi requer a ação de várias moléculas ativadoras e reguladoras, que muitas vezes são expressas de forma concomitante. A expressão orquestrada de cada uma dessas moléculas permite o desenvolvimento das várias etapas da resposta imune na malária. / Malaria is among the most prevalent diseases in the world, affecting approximately 500 million people per year. It is known that the pro-inflammatory response provides the control of parasitemia, but also triggers the clinical manifestations that are directly related to the fatal cases of the disease. The analyzes in mice infected with 106 erythrocytes parasitized with Plasmodium chabaudi AS show that, in the acute phase of malaria, there is an intense proliferation with detectable parasitemia on day 4 post-infection (p .i.), being the peak attained at day 7 p.i. and the decline until day 10 p.i .. Following the kinetics of the parasite, there is an increase in the total number of splenocytes. The activation of the immune system is characterized by a Th1 profile, with expansion of the populations of conventional CD4+ T cells and CD4+ Foxp3+ regulatory (Treg) T cells and predominant production of IFN-g. In this study, we evaluated in mice infected with P. chabaudi AS: 1} The expression profile of molecules with key roles in the immune responses of conventional CD4+ T cells and Treg cells; 2} The effects of in vitro inhibition of ICOS and OX40 molecules in the proliferative responses both cell populations that were stimulated with parasitized erythrocytes; 3} The suppressive activity of Treg cells on the conventional CD4+ T cells. The results showed that, from day 4 p.i. on, there was an increase in the percentages of conventional CD4+ T cells and Treg cells that expressed stimulatory GITR, OX40 and ICOS molecules. We also observed a correlation between the higher expression of CD25 with the increase of 0ther activation molecules that were present in conventional CD4+ T cells, a phenomenon less pronounced in Treg cells. By inhibiting the activity of ICOS and OX40 molecules, we observed that ICOS inhibition interfered more intensely in the proliferation of the Treg cell population, while the inhibition of OX40 dramatically reduced the proliferation of conventional CD4+ T cells and Treg cells. The suppression assays indicated that ICOS+ Treg cells were more effective to control the proliferation of conventional CD4+ T cells. Furthermore, we observed that, in the spleen of P. chabaudi-infected mice, there was an increase in the percentage of conventional CD4+ T cells expressing PD-1 and PD-L 1. However, in Treg cells, we detected a reduction in the expression of PD-1 and increase of PD-L 1, providing evidence about the mechanism that may be involved in the control of cell numbers in the acute phase of infection. We also observed that, during the expansion of CD4+ T cells, there was no change in the percentage of cells expressing CTLA-4 or the levei of expression of this molecule on the various days of infection. Considering the data together, we concluded that the modulation of the immune response to malaria caused by P. chabaudi requires the action of several activating and regulatory molecules, which are often expressed concomitantly. The orchestrated expression of each of these molecules allows the development of the various stages of the immune response to malaria.

Os linfócitos, principais células do sistema imune, podem ser encontrados em órgãos e tecidos de dois grandes sistemas do corpo: o sistema linfático, composto por uma extensa rede de vasos linfáticos e linfonodos; e o sistema linfoide, mais abrangente e que, além de englobar o sistema linfático, abrange todas as células, tecidos e órgãos do corpo que contêm agregados linfocitários, tais como o timo, baço e linfonodos. Embora esteja amplamente descrito para animais domésticos e alguns animais silvestres, estudos sobre o sistema imune em cetáceos são escassos. A influência negativa de contaminantes no sistema imune em mamíferos aquáticos está em constante discussão. Assim, um conhecimento mais profundo da anatomia deste sistema é essencial para a interpretação clínica e de achados de necropsia, para uma melhor compreensão dos achados patológicos. Portanto, o objetivo deste estudo foi caracterizar morfológica e ultraestruturalmente os órgãos do sistema linfoides de odontocetos de ocorrência no litoral brasileiro. As amostras utilizadas foram procedentes de animais encalhados nas regiões norte e nordeste do Brasil. Os órgãos analisados foram baço, timo e linfonodo, bem como os tecidos linfoides associados à mucosa. Primeiramente as amostras foram localizadas topograficamente e avaliadas macroscopicamente. Posteriormente, as amostras foram fixadas e analisadas por microscopias de luz, eletrônica de varredura e transmissão, imunohistoquímica e histomorfometria. Através das análises realizadas foi possível observar que os órgãos e tecidos linfoides em cetáceos são semelhantes ao observado em mamíferos domésticos, com algumas particularidades. Não existem diferenças morfológicas com relação ao timo entre as espécies estudadas, com exceção da não existência de tecido adiposo substituindo o órgão em animais mais jovens, e a presença de Corpúsculos de Hassal mais evidentes em tamanho neste grupo. Novos grupos de linfonodos foram descritos de acordo com a sua localização, entretanto todos possuiram arquitetura semelhante ao descrito na literatura para mamíferos terrestres. Os linfonodos estavam dispostos de forma solitária ou em grupos e apresentavam formato variado, recobertos por uma cápsula, e o parênquima do órgão dividiu-se em região cortical e medular. Os centros germinativos apresentaram-se mais evidentes e desenvolvidos em animais filhotes e jovens. Os baços e baços acessórios eram morfologicamente semelhantes, caracterizados por numerosos nódulos linfáticos delimitados pela bainha linfoide periarterial e uma rede celular difusa que circundava os nódulos linfáticos, sem diferenciação entre as camadas cortical e medular. Centros germinativos se tornaram mais discretos e reduzidos em número com o aumento da idade. Os baços acessórios estavam firmemente aderidos ao baço e/ou à grande curvatura da primeira cavidade do estômago, sendo mais prevalentes em animais com maior escore corporal e de mergulhos mais profundos, sugerindo uma função de reservatório sanguíneo complementar. Os tecidos linfoides associados à mucosa em cetáceos foram semelhantes aos observados em mamíferos terrestres, com adaptações inerentes ao meio aquático, como a presença de tonsilas orofaríngea e anal, assegurando uma resposta imunológica mais eficiente diante de desafios antigênicos constantes presentes em seu habitat. Sugere-se que este segmento do sistema linfoide é essencial para a proteção do animal diante dos contaminantes presentes em seu habitat. Com base nos achados do presente estudo, será possível uma melhor compreensão do funcionamento e estrutura do sistema imunológico das espécies estudadas, colaborando na elucidação das causas de encalhe destes animais, que poderão funcionar como potenciais indicadores ambientais / Lymphocytes, key cells of the immune system, can be found in organs and tissues of two major systems of the body: the lymphatic system, composed of an extensive network of lymph vessels and lymph nodes; and the lymphoid system, more comprehensive that, in addition to comprise the lymphatic system, includes all cells, tissues and organs containing lymphoid aggregates, such as the thymus and spleen. Although these systems are widely described in domestic animals and some wildlife species, studies about marine mammals are scarce. The negative influence of contaminants in the immune system of aquatic mammals is in constant discussion. The knowledge on the anatomy of these systems is essential for clinical interpretation and necropsy, providing a better understanding of the pathological findings. Therefore, the aim of this study was to characterize the morphology and ultrastructure of lymphoid system of odontocetes occurring in the Brazilian coast. Samples from animals stranded in the northern and northeastern regions of Brazil were collected and organs spleen, thymus and lymph node and mucosa-associated lymphoid tissue were analyzed. First, all samples were evaluated macroscopically and topographically located. Subsequently, they were fixed and analyzed by light microscopy, scanning electron and transmission, immunohistochemistry and histomorphometry. Through these analyzes it was observed that the organs and lymphoid tissues in cetaceans are similar to that observed in domestic mammals, with some peculiarities inherent to their habitat. There were no morphological differences from the thymus in the species studied, except for the absence of adipose tissue replacing the organ in younger animals, and the presence of Hassall corpuscles more prominent in this group. New groups of lymph nodes were described, possessing architecture similar to that described in the literature for terrestrial mammals. Lymph nodes were arranged solitarily or in groups and had varied format, covered by a capsule and the parenchyma of the organ was divided into cortical and medullary region. Their germinal centers had become more evident and developed in puppies and young animals. Spleens and accessory spleens were morphologically similar, characterized by numerous lymph nodules delimited by periarterial lymphoid sheath and a diffuse cellular network in its surrounding area, without differentiation between cortical and medullary layers. Germinal centers became more discrete and reduced in number with increasing age. Accessory spleens were firmly adhered to the spleen and / or the greater curvature of the first stomach and were more prevalent in animals with higher body score and dives deeper, suggesting a role of complement blood reservoir. The mucosa-associated lymphoid tissues in cetaceans were similar to those observed in terrestrial mammals, with inherent aquatic adaptations, such as the presence of oropharyngeal and anal tonsils, ensuring a more efficient immune response in the face of constant antigenic challenges present in their habitat. It is suggested that this segment of the lymphoid system is essential for the protection of the animal before the contaminants in their habitat. Based on these findings, this study will enable a better understanding of the structure and functioning of the immune system of the species studied, collaborating in the elucidation of causes of stranding of these animals, whicih may act as potential environmental indicators

O presente trabalho visa, através de métodos genético-epidemiológicos, identificarem genes associados à resposta ao antígeno da Leishmania. Utilizando amostras através do teste de Montenegro dos municípios de Monte Negro (RO) e Assis Brasil (AC). Na primeira abordagem foram feitos testes com TaqMan&#210 e a segunda com GWAS, e análises de associação foram feitas utilizando-se o pacote SPSS e o Plink. Não foram encontradas associações com cinco SNPs (MYD88, IL12, IL10, IFNGR1 e NRAMP1). A análise de dados de varredura genômica com filtros, indicou uma região no cromossomo 10 com 3 SNPs próximos que fazem parte de uma região regulatória que com o posterior auxilio do real time não se confirmaram, apesar do ensaio RS11251056 apresentar valores limítrofes, se tornando uma possível indicação para trabalhos futuros e por fim a último teste foi a meta-análise, através do método de Woolf, apresentou resultados indicativos de associação para ensaios encontrados no cromossomo 2 com ZNF638 relacionados a diferenciação celular e também no cromossomo 10 que contem lincRNAs e o gene NGR3, com dois ensaios apresentando valores significativos de p, onde podemos inferir que estas duas regiões podem participar ativamente na diferenciação da resposta ao antígeno da Leishmania. / The present study aims, through genetic-epidemiological methods, to identify genes associated with response to Leishmania antigen. Using samples Montenegro skin test through the municipalities of Monte Negro (RO) and Assis Brazil (AC). In the first approach were tested with TaqMan&#210 and the second GWAS, and association analyzes were performed using SPSS and Plink. No associations were found with five SNPs (MyD88, IL12, IL10, IFNGR1, and NRAMP1). The analysis of genome scan data with filters, indicated a region on chromosome 10 with three nearby SNPs that are part of a regulatory region that later with the help of real time is not confirmed, although the test rs11251056 have borderline values, becoming an possible direction for future work and finally the last test was the meta-analysis by the method of Woolf, presented results indicating the association found in tests for chromosome 2 with ZNF638 related to cell differentiation and also on chromosome 10 that contains lincRNAs and gene NGR3, two runs with a significant p value, where we can infer that these two regions can actively participate in the differentiation of the response to Leishmania antigen.

Key Points: (1) Nutrition management for individuals infected with HIV can be helpful in maintaining lean body weight, combating oxidative stress, reducing complications from hyperglycemia and hyperlipidemia, and managing gastrointestinal function. (2) Patients may need to be individualized to meet each individual's unique requirements. (3) Consideration should be given to including the expertise of a registered dietitian/nutritionist s part of the health care team to promote wellness in the individuals infected with HIV.

Pentraxin 3 (PTX3) is a vital regulator of innate immune function that has been shown to counterregulate pro-inflammatory signaling and protect against the development of cardiovascular disease (CVD). Less is known about how PTX3 may mitigate against CVD risk by regulating the pro-inflammatory response at the cellular level. Therefore, this dissertation details four manuscripts which aimed to examine the capacity of PTX3 to regulate the innate immune response of peripheral blood mononuclear cells (PBMCs) isolated from healthy adults. Manuscript 1 examined the capacity of PTX3 to alter the inflammatory milieu following in vitro stimulation of isolated PBMCs with the pro-inflammatory lipid palmitate. In addition, Manuscript 2 sought to examine how participation in acute exercise, a powerful anti-inflammatory behavior that reduces CVD risk, alters the inflammatory phenotype and response of mononuclear cells following ex vivo stimulation with lipopolysaccharide (LPS). Manuscript 3 aimed to further elucidate the potential impact of cardiorespiratory fitness on the capacity of PTX3 to stimulate an innate immune response prior to and immediately following acute exercise in aerobically trained and untrained individuals. Finally, Manuscript 4 investigated the impact of healthy aging on plasma PTX3 concentrations and its relationship with telomere length in middle-aged compared to young adults. The capacity of isolated PBMCs to express a key cellular mechanism involved in maintaining longer telomere lengths, human telomerase reverse transcriptase (hTERT), following cellular stimulation with LPS, PTX3, and PTX3+LPS was also examined to address a mechanism that might explain how persistent exposure of circulating immune cells to the age-related pro-inflammatory milieu contributes to the shortening of telomere lengths.

Decellularized extracellular matrices have been a growing area of interest in the biomedical engineering fields of tissue engineering and regenerative medicine.As these materials move toward clinical applications, the immune response to these materials will be a driving force toward their success in clinical approaches. Fully digested decellularized matrix constructs derived from porcine liver, muscle and lung were created to test the adaptive immune response. Hydrogel characterization ensured that the materials had relatively similar stiffness levels to reduce variability, and in vitro studies were conducted. Each individual construct as well as a gelatin control were plated with a co-culture of macrophages and T-cells to measure T-cell proliferation. In addition standard markers of inflammation through qPCR were measured in the macrophage group. Constructs were then placed into animals for 3 and 7 days in addition to a second group that received constructs for 21 days before secondary constructs were placed. These groups were then sacrificed following 3, 7 and 14 days to measure the residual and memory-like response of the constructs. Our results showed that t-cell proliferation was increased with decellularized constructs, particularly in tissue with higher DNA content. In vivo, animals with secondary treatments showed extended inflammatory response, driven by Th1 and Th17 polarization suggesting a memory-like response due to recognition of peptides in the constructs from secondary placements.

Currently, the Caribbean has the second highest new cases of HIV infection, only after Sub-Saharan Africa. Women are becoming disproportionally more at risk for HIV/AIDS, mainly through heterosexual contact. The purpose of this dissertation study was to evaluate HIV knowledge, attitudes, and sexual risk behaviors among Trinidadian women. A sample of 113 participants was recruited for this study. The Theory of Planned Behavior (TPB) and Purnell Model of Cultural Competence were used to guide this study. Data were gathered using the HIV Knowledge Questionnaire (HIV-KQ-18), Condom Attitude Scale (CAS), Safe Sex Behavior Questionnaire (SSBQ), and a demographic questionnaire. Data were analyzed using statistical analysis software package (SPSS) version 22. Descriptive and Frequencies, Pearson product-moment correlation coefficient (r), one-way between groups ANOVA, and Multiple Regression analyses were implemented to assess HIV knowledge, attitudes about condom use, religious beliefs, level of education, and substance use among Trinidadian women. The results of this study indicated that level of education and race/ethnic backgrounds were associated with HIV knowledge among Trinidadian women. Religious beliefs had a negative correlation with attitudes about condom use. Also, there was a positive correlation between attitudes about condom use and safer sexual behaviors. The empirical knowledge obtained from this study can be used to provide a baseline for healthcare providers and policy makers to develop culturally aware, gender-relevant interventions to decrease the rate of HIV infection among Trinidadian women.

Network security has always been an area of priority and extensive research. Recent years have seen a considerable growth in experimentation with biologically inspired techniques. This is a consequence of our increased understanding of living systems and the application of that understanding to machines and software. The mounting complexity of telecommunications networks and the need for increasing levels of security have been the driving factor. The human body can act as a great role model for its unique abilities in protecting itself from external, foreign entities. Many abnormalities in the human body are similar to that of the attacks in wireless sensor networks (WSN). This paper presents basic ideas drawn from human immune system analogies that can help modelling a system to counter the attacks on a WSN by monitoring parameters such as energy, frequency of data transfer, data sent and received. This is implemented by exploiting two immune concepts, namely danger theory and negative selection. Danger theory aggregates the anomalies based on the weights of the anomalous parameters. The objective is to design a cooperative intrusion detection system (IDS) based on danger theory. Negative selection differentiates between normal and anomalous strings and counters the impact of malicious nodes faster than danger theory. We also explore other human immune system concepts and their adaptability to Wireless Sensor Network Security.

L'inflammation chronique en réponse à l'accumulation de lipoprotéines dans la paroi artérielle est centrale dans le développement de l'athérosclérose. L’immunité innée et adaptée sont impliquées dans ce processus. Les cellules Natural Killer (NK), un des éléments clés de l'immunité innée, ont été identifiées dans les lésions athérosclérotiques humaines et murines. Bien que plusieurs études aient cherché à évaluer le rôle des cellules NK dans des modèles animaux expérimentaux d'athérosclérose, les résultats restent contradictoires, certaines rapportant des effets pro-athérogéniques, d’autres anti-athérogéniques. L'une des principales limites de ces études est le manque de spécificité dans le ciblage de la perte ou du gain de fonction des cellules NK. Nous avons utilisé deux approches génétiques sélectives pour étudier le rôle des cellules NK dans l'athérosclérose: 1) des souris Ncr1iCre/+R26lslDTA/+ dans lesquelles les cellules NK ont été déplétées 2) des souris Noé, dont les cellules NK sont hyper-réactives. Les cellules de la moelle osseuse (BM) de ces souris ont été utilisées pour reconstituer le système hématopoïétique de souris Ldlr -/- irradiées. Après une période de récupération de 4 semaines, les souris ont été mises sous un régime riche en matières grasses (HFD) pendant 8 semaines. L'analyse morphométrique de la taille des lésions ‘athérosclérose dans le sinus aortique et l'aorte thoracique n'a montré aucune différence statistiquement significative entre les 3 groupes. De plus, aucune différence n'a été observée dans la composition de la plaque en termes de teneur en collagène, d'infiltration de macrophages ou de profil immunitaire dans le sang et la rate des souris Ncr1iCreR26lsl-DTA, Noé ou contrôles. Nous avons ensuite étudié la sélectivité de des anticorps anti-asialo-GM1 dans la déplétion des cellules NK, qui avaient été utilisés précédemment pour démontrer le rôle pro-athérogène des cellules NK. Nous avons confirmé les effets non spécifiques de cet anticorps, qui déplète non seulement les cellules NK, mais aussi les lymphocytes NKT et CD8+. Enfin, pour déterminer si l'activation des cellules NK par un stimulus externe pouvait avoir des effets sur l’athérosclérose, nous avons traité les souris chimériques (souris Ldlr -/- irradiées reconstituées soit avec les cellules de moelle contrôle ou déficiente en cellules NK) avec du poly IC (un mimétique viral) pendant 8 semaines de HFD. Nous avons trouvé une réduction significative de la taille des lésions au niveau du sinus aortique et de l'aorte thoracique dans les souris déficientes en cellules NK. Nos résultats, à partir de modèles de souris spécifiques, contredisent les études antérieures et démontrent clairement que chez les souris hypercholestérolémiques, les cellules NK n'ont aucun effet direct sur l'athérosclérose, sauf si elles sont pré-stimulée, comme par exemple dans un contexte d’infection virale ou de présence de tumeurs. / Chronic inflammation is central in the development of atherosclerosis. Both innate and adaptive immunity are involved in this process. Although several studies have evaluated the functions of NK cells in experimental animal models of atherosclerosis, it is not yet clear whether NK cells behave as protective or pro-atherogenic effectors. One of the main caveats of previous studies was the lack of specificity in targeting loss- or gain-of-function of NK cells. Here, we used two selective genetic approaches to investigate the role of NK cells in atherosclerosis: 1) Ncr1iCre/+R26lslDTA/+ mice in which NK cells were depleted, 2) Noé mice in which NK cells are hyperresponsive. No difference in atherosclerotic lesion size was found in Ldlr-/- mice transplanted with bone marrow cells from Ncr1iCreR26Rlsl−DTA, Noé or WT mice. Also, no difference was observed in plaque composition in terms of collagen content, macrophage infiltration or the immune profile in blood and spleen, although Noé chimera had more IFN-y-producing NK cells in comparison with WT mice. Then, we investigated the NK cell selectivity of anti-asialo GM1 anti-serum, which was previously used to conclude to the pro-atherogenicity of NK cells. Anti-asialo GM1 treatment decreased atherosclerosis in both Ldlr-/- mice transplanted with Ncr1iCreR26Rlsl−DTA or WT BM, indicating that its anti-atherogenic effects are unrelated to NK cell depletion. Finally, to determine whether NK cells could contribute to the disease in conditions of pathological NK cell overactivation, we treated irradiated Ldlr-/- mice reconstituted with either WT or Ncr1iCreR26Rlsl−DTA BM with the viral mimic Poly(I:C) and found a significant reduction of plaque size in NK-cell deficient chimeric mice. Our findings, using state-of-the-art mouse models, clearly demonstrate that NK cells have no direct effect on the natural development of hypercholesterolemia-induced atherosclerosis, but may play a role when an additional systemic NK cell overactivation occurs.