Orientador: Tereza Cristina Cardoso da Silva / Banca: Roberto Gameiro de Carvalho / Banca: Luiz Eduardo Corrêa Fonseca / Banca: Andrea Fontes Garcia / Banca: Lídia Luciana Ravagnani / Resumo: O Brasil possui um dos maiores rebanhos de bovinos mundialmente. Estes animais estão expostos constantemente a agentes virais causadores de patologias. Dentre estes, o herpesvírus bovino 1 (BHV1) e 5 (BHV5) apresentam grande importância epidemiológica. O BHV1 causa infecções respiratórias e genitais, enquanto que o BHV5 meningoencefalite. As proteínas de membrana presentes nos herpesvírus os tornam capazes de infectar as células do hospedeiro. Com afinidade a distintas células, desenvolvem sua capacidade de infecção, apresentam mecanismos de sobrevivência à morte celular programada e a resposta imunológica. As interações vírus-hospedeiro são fundamentais no entendimento de aspectos relacionados a transmissão viral, capacidade de infecção e progressão da doença. Para este fim, se faz necessário compreender elementos fundamentais, como a modulação da função mitocondrial e a replicação do BHV, bem como os níveis de apoptose nas células do hospedeiro. De igual importância, é indispensável entender o comportamento de genes apoptóticos que estão relacionados à infecção por BHV5 e seus envolvimentos na viabilidade celular. Estes achados contribuem para o entendimento da imunopatogenia do BHV, auxiliam a evitar a disseminação destes agentes e são de grande valia para o desenvolvimento de vacinas / Abstract: Brazil has one of the largest cattle hers worldwide. These animals are constantly exposed to pathological viral agents. Bovine herpesvirus 1 (BHV1) and BHV5 have great epidemiological importance. BHV1 is causative agent of respiratory and genital infections, while BHV5 causes meningoencephalitis. Herpesvirus membrane proteins allow them to infect the host cells. They present affinity to different types of cells, develop mechanisms to survive programmed cell death, and immune response. Virus-host interactions are essential to understand aspects related to viral transmission, capacity of infection and disease progression. To this end, it is necessary to understand the fundamental elements related to the modulation of mitochondrial function and replication of BHV, as well as apoptosis levels in the host cells. It is crucial to understand the behavior of apoptotic genes related to BHV5 infection and cell viability. These findings contribute to understanding the BHV immunopathogenesis, help to prevent the spread of these agents, and are of great value to the development of vaccines / Doutor

Although Rhodococcus equi (R. equi), previously known as Corynebacterium equi, was first isolated from pneumonic foals almost a century ago, it remains the most common cause of subacute or chronic granulomatous bronchopneumonia in foals. While the majority of foals exposed to R. equi develop a protective immune response (regressors), others exhibit a unique susceptibility to infection (progressors). The determinants for either outcome are not completely understood. Therefore, current diagnostic and preventive measures are suboptimal and require betterment. In light of this current need, we hypothesized that immunoglobulin G subisotype T [IgG(T)] against the virulence-associated protein A (VapA) of R. equi, and whole blood cytokine expression profile of foals predict the outcome of infection and can be used as diagnostic markers of clinical disease. Further, we hypothesized that the use of R. equi hyperimmune plasma (HIP) decreases severity of disease in naturally infected foals, playing an important role in disease prevention in the field. Lastly, we hypothesized that specific anti-Rhodococcus equi pili antibodies passively acquired by foals via colostrum after immunization of pregnant mares with a Rhodococcus equi pili-based candidate vaccine will confer protection against induced disease, and therefore have an immediate impact on R. equi pneumonia prophylaxis. The objectives of this study were: (1) to describe the humoral immune response of progressor and regressor foals to R. equi following experimental challenge and natural infection, (2) to compare the cytokine and cell-marker expression profile in whole blood of progressor and regressor foals after challenge, (3) to evaluate the Vap-A specific IgG profile of a commercially available HIP product and its value as a prophylactic tool on an endemic farm, and (4) to evaluate the efficacy of a vaccine based on the Rhodococcus equi pili (Rpl). Although the IgG(T) response of progressor foals after challenge or following natural infection tended to be more pronounced than that observed in regressor foals, its performance as a diagnostic test for predicting disease outcome was poor. Likewise, whole blood cell-marker and cytokine expression profiles of progressor and regressor foals were not significantly different, undermining its reliability as a diagnostic tool. Evaluation of the association of HIP VapA specific IgG profile and rhodococcal disease outcome in the field resulted in the conclusion that progressor foals received significantly less VapA specific IgG, suggesting that HIP may have provided some protection to regressor foals. Although HIP appeared to have provided some protection against clinical pneumonia, Rpl maternally-derived IgG failed to confer any advantage to foals born from vaccinated mares. The Rpl candidate vaccine failed to confer protection to foals after challenge, and did not decrease disease severity in comparison to a control group. In summary, the results of this study do not support the use of VapA specific IgG(T) or whole blood cytokine expression profile as predictors of disease outcome. Further, our results suggest a positive effect of HIP on disease outcome. Lastly, the presence of systemic and local Rpl antibodies was not protective in foals.

Herpes simplex virus (HSV) infection of the cornea leads to a blinding immuno-inflammatory condition of the eye also called stromal keratitis (SK). SK immunopathology is characterized by the infiltration of CD4+ T cells of Th1 phenotype as well as the development of new blood vessels into the normally avascular cornea. Studies in mouse models of SK have firmly established the role of CD4+ T cells, and particularly of Th1 phenotype, as the principal mediators of SK immunopathology. However, with the recent discovery of IL-17A and Th17 cells, the role of this cytokine as well as Th17 cells remains to be further defined. Recently it was shown that the normal cornea expresses VEGF-A, however its biological activity is impeded by its binding to a soluble form of VEGF-A receptor-1 (sVEGFR-1). Past studies have implicated the role of vascular endothelial growth factor-A (VEGF-A) in HSV induced corneal angiogenesis, however the source of VEGF-A as well as molecular mechanisms, particularly in the context of VEGF-A/sVEGFR-1 balance during HSV infection, are poorly understood. The first part of this dissertation (I) reviews past literature on HSV induced corneal SK immunopathology. It focuses on the understanding of HSV-1 induced events that particularly results in corneal angiogenesis as well as tissue damage mediated by different type of cells as well as their secreted products. The next three parts (II-IV) focus on the mechanisms of HSV induced corneal angiogenesis as well as the relative role of Th1 and Th17 cells in SK immunopathology. Results in part II focuses on the relative role of IFN-γ/IL-17 as well as Th1/Th17 cells in HSV induced corneal immunopathology. The third section evaluate the significance of VEGF-A/sVEGFR-1 balance in HSV induced corneal neovascularization. Results in part IV focus on the role of IL-17A in altering the balance between VEGF-A and sVEGFR-1 post ocular HSV infection and subsequent corneal angiogenesis. Collectively these studies identified novel mechanisms by which HSV infection of the cornea leads to the development of angiogenesis as well as corneal tissue damage and subsequent SK immunopathology, the most common cause of infectious blindness in the Western World.

Made available in DSpace on 2014-08-27T14:36:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-07-15Bitstream added on 2014-08-27T15:57:17Z : No. of bitstreams: 1 000779820.pdf: 7636663 bytes, checksum: 221e2960f370d289d0928952e2d4eb9c (MD5) / É sabido que alguns patógenos podem desencadear o processo de apoptose em determinadas células do organismo, entretanto, o BHV-5 inibe a apoptose em embriões bovinos com sete dias de desenvolvimento. Por esta razão, o objetivo deste trabalho foi investigar a interação vírus-embrião no mecanismo de morte celular programada. Oócitos bovinos foram divididos em dois grupos, sendo: I (controle) e II (exposto ao BHV-5). Após 24 horas de maturação in vitro, 100 oócitos de cada grupo foram desnudados e observados em microscópio invertido para verificação da extrusão do primeiro corpúsculo polar, sendo o restante dos oócitos incubados com espermatozoides, por 18 a 20 horas, para que ocorresse o processo de fertilização in vitro. Transcorrido este período, os prováveis zigotos foram desnudados e transferidos para gotas contendo meio de cultivo (mSOF), até o dia sete pós-inseminação. Os embriões produzidos in vitro foram submetidos à técnica de PCR em tempo real para pesquisa do BHV-5 e análise da transcrição dos genes Mcl-1, Bax, caspase-2, -3 e Apaf-1 relacionados à apoptose, além do teste de MTT ((3-[4,5dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)), para avaliação da atividade mitocondrial. A análise estatística para a taxa de maturação nuclear dos oócitos foi feita pelo teste de x2. A produção in vitro de embriões, MTT e transcrição gênica foi avaliada pelo teste t não pareado. Observou-se que o BHV-5 não interferiu na taxa de maturação nuclear dos oócitos e no desenvolvimento embrionário, entretanto os embriões do grupo I apresentaram maior viabilidade mitocondrial e os embriões do grupo II tiveram a expressão dos genes Bax e caspase-2 diminuídos, comprovando que o vírus inibiu o processo de morte celular programada nos embriões bovinos sete dias pósinseminação, a fim de favorecer a disseminação viral / It is known that some pathogens can initiate apoptosis in certain cells of the organism, however, BHV-5 inhibits apoptosis in bovine embryos after seven days of development. Therefore, the aim was to investigate the interaction virus-embryo in the mechanism of programmed cell death. Bovine oocytes were divided into two groups: I (control) and II (exposed to BHV-5). After 24 hours of in vitro maturation, 100 oocytes of each group were denuded and observed under inverted microscope to check the extrusion of the first polar body, and the other oocytes were incubated with spermatozoa for 18 to 20 hours, for in vitro fertilization. After this period, presumptive zygotes were denuded and transferred to drops containing culture medium (mSOF), until day seven postfertilization. In vitro produced embryos were submitted to real time PCR to evaluated the presence of BHV-5 and expression of Mcl-1, Bax, caspase-2, -3 and Apaf-1 related to apoptosis, also the MTT assay ((3 - [4,5-dimethylthiazol 2-yl] -2,5-diphenyl tetrazolium bromide)) was performed for the evaluation of mitochondrial activity. Statistical analysis for nuclear maturation of oocytes was performed by x2 test. In vitro embryo production, MTT and gene expression were analyzed by unpaired t test. It was observed that BHV-5 did not influence nuclear maturation rate of oocytes or embryonic development, however embryos of group I showed greater mitochondrial viability, and embryos of group II had a decrease in genes expression of Bax and caspase-2, suggesting that the virus inhibited the process of programmed cell death in bovine embryos seven days post-fertilization, in order to promote viral spread

Made available in DSpace on 2014-12-02T11:16:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-10-16Bitstream added on 2014-12-02T11:21:23Z : No. of bitstreams: 1 000793685_20151016.pdf: 161710 bytes, checksum: 4a9f0001ff3f02b0d79ee5f3b8e81a53 (MD5) Bitstreams deleted on 2015-10-16T13:53:57Z: 000793685_20151016.pdf,. Added 1 bitstream(s) on 2015-10-16T13:54:45Z : No. of bitstreams: 1 000793685.pdf: 777527 bytes, checksum: 7cacdf2227f058a27d3c518a2de98480 (MD5) / Nos últimos anos, a emergência de Salmonella Senftenberg no ambiente de granjas de frango tornou-se causa de preocupação, pois este sorotipo, além de ser um potencial agente de paratifo aviário em condições de estresse, tem sido associado a diversos casos de infecções humanas. Acredita-se que sua ampla disseminação seja resultado da capacidade de formar biofilmes, resistir à desidratação, acidez, temperaturas elevadas e radiação, além de permanecer por longos períodos no ceco das aves, na ração e no ambiente. Devido a estas peculiaridades, o controle de Salmonella Senftenberg é um desafio para a avicultura e exige a adoção de medidas de controle baseadas no conhecimento das rotas de disseminação e na biologia do micro-organismo. Neste estudo, a disseminação de Salmonella Senftenberg em granjas de frango, localizadas na região noroeste do estado de São Paulo, foi avaliada usando a tipagem molecular pela técnica de Pulsed Field Gel Electrophoresis (PFGE). Os dados epidemiológicos foram utilizados como ferramenta auxiliar para a comparação dos perfis de PFGE das cepas. As Salmonella Senftenberg isoladas de ingredientes de ração, ambiente de fábrica de ração, aves, ambiente dos aviários e de animais provenientes dos arredores de granjas avícolas, apresentaram diferentes identidades genéticas, indicando a transmissão de genótipos distintos entre as várias localidades / In the last years, Salmonella Senftenberg has become an emerging pathogen affecting broiler farm’s environment and figuring many concerns. In addition to be considered as potential agent of avian paratyphoid under stress conditions, this serotype has been associated to vast cases of human infections. It is supposed its wide dissemination is due to the capacity to produce biofilm, resist to dehydration, lower pH, high temperatures and radiation, and remain for long periods in the bird ceca, feed and environment. Because of these peculiarities, Salmonella Senftenberg control shows as a challenge for the poultry industry and requires the adoption of many procedures based on understanding its dissemination routes and biological cycle. In this study, Salmonella Senftenberg spread in broiler farms located in the northwestern part of São Paulo State was assessed using molecular typing by PFGE. The epidemiology data was used as an extra tool for strain comparison. Salmonella Senftenberg isolated from feed ingredients, feed mill environment, birds, poultry houses and wildlife surround poultry facilities, showed different genetic identities, indicating transmission of different genotypes between various locations

Orientador: Mara Corrêa Lelles Nogueira / Banca: Maria Teresa Destro / Banca: Alessandra Vidotto / Resumo: Nos últimos anos, a emergência de Salmonella Senftenberg no ambiente de granjas de frango tornou-se causa de preocupação, pois este sorotipo, além de ser um potencial agente de paratifo aviário em condições de estresse, tem sido associado a diversos casos de infecções humanas. Acredita-se que sua ampla disseminação seja resultado da capacidade de formar biofilmes, resistir à desidratação, acidez, temperaturas elevadas e radiação, além de permanecer por longos períodos no ceco das aves, na ração e no ambiente. Devido a estas peculiaridades, o controle de Salmonella Senftenberg é um desafio para a avicultura e exige a adoção de medidas de controle baseadas no conhecimento das rotas de disseminação e na biologia do micro-organismo. Neste estudo, a disseminação de Salmonella Senftenberg em granjas de frango, localizadas na região noroeste do estado de São Paulo, foi avaliada usando a tipagem molecular pela técnica de Pulsed Field Gel Electrophoresis (PFGE). Os dados epidemiológicos foram utilizados como ferramenta auxiliar para a comparação dos perfis de PFGE das cepas. As Salmonella Senftenberg isoladas de ingredientes de ração, ambiente de fábrica de ração, aves, ambiente dos aviários e de animais provenientes dos arredores de granjas avícolas, apresentaram diferentes identidades genéticas, indicando a transmissão de genótipos distintos entre as várias localidades / Abstract: In the last years, Salmonella Senftenberg has become an emerging pathogen affecting broiler farm's environment and figuring many concerns. In addition to be considered as potential agent of avian paratyphoid under stress conditions, this serotype has been associated to vast cases of human infections. It is supposed its wide dissemination is due to the capacity to produce biofilm, resist to dehydration, lower pH, high temperatures and radiation, and remain for long periods in the bird ceca, feed and environment. Because of these peculiarities, Salmonella Senftenberg control shows as a challenge for the poultry industry and requires the adoption of many procedures based on understanding its dissemination routes and biological cycle. In this study, Salmonella Senftenberg spread in broiler farms located in the northwestern part of São Paulo State was assessed using molecular typing by PFGE. The epidemiology data was used as an extra tool for strain comparison. Salmonella Senftenberg isolated from feed ingredients, feed mill environment, birds, poultry houses and wildlife surround poultry facilities, showed different genetic identities, indicating transmission of different genotypes between various locations / Mestre

Orientador: Tereza Cristina Cardoso / Banca: Helena Lage Ferreira / Banca: Vera Claúdia Magalhães Curci / Banca: Flávia Lombardi Lopes / Banca: Roberto Gameiro de Carvalho / Resumo: É sabido que alguns patógenos podem desencadear o processo de apoptose em determinadas células do organismo, entretanto, o BHV-5 inibe a apoptose em embriões bovinos com sete dias de desenvolvimento. Por esta razão, o objetivo deste trabalho foi investigar a interação vírus-embrião no mecanismo de morte celular programada. Oócitos bovinos foram divididos em dois grupos, sendo: I (controle) e II (exposto ao BHV-5). Após 24 horas de maturação in vitro, 100 oócitos de cada grupo foram desnudados e observados em microscópio invertido para verificação da extrusão do primeiro corpúsculo polar, sendo o restante dos oócitos incubados com espermatozoides, por 18 a 20 horas, para que ocorresse o processo de fertilização in vitro. Transcorrido este período, os prováveis zigotos foram desnudados e transferidos para gotas contendo meio de cultivo (mSOF), até o dia sete pós-inseminação. Os embriões produzidos in vitro foram submetidos à técnica de PCR em tempo real para pesquisa do BHV-5 e análise da transcrição dos genes Mcl-1, Bax, caspase-2, -3 e Apaf-1 relacionados à apoptose, além do teste de MTT ((3-[4,5dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide)), para avaliação da atividade mitocondrial. A análise estatística para a taxa de maturação nuclear dos oócitos foi feita pelo teste de x2. A produção in vitro de embriões, MTT e transcrição gênica foi avaliada pelo teste t não pareado. Observou-se que o BHV-5 não interferiu na taxa de maturação nuclear dos oócitos e no desenvolvimento embrionário, entretanto os embriões do grupo I apresentaram maior viabilidade mitocondrial e os embriões do grupo II tiveram a expressão dos genes Bax e caspase-2 diminuídos, comprovando que o vírus inibiu o processo de morte celular programada nos embriões bovinos sete dias pósinseminação, a fim de favorecer a disseminação viral / Abstract: It is known that some pathogens can initiate apoptosis in certain cells of the organism, however, BHV-5 inhibits apoptosis in bovine embryos after seven days of development. Therefore, the aim was to investigate the interaction virus-embryo in the mechanism of programmed cell death. Bovine oocytes were divided into two groups: I (control) and II (exposed to BHV-5). After 24 hours of in vitro maturation, 100 oocytes of each group were denuded and observed under inverted microscope to check the extrusion of the first polar body, and the other oocytes were incubated with spermatozoa for 18 to 20 hours, for in vitro fertilization. After this period, presumptive zygotes were denuded and transferred to drops containing culture medium (mSOF), until day seven postfertilization. In vitro produced embryos were submitted to real time PCR to evaluated the presence of BHV-5 and expression of Mcl-1, Bax, caspase-2, -3 and Apaf-1 related to apoptosis, also the MTT assay ((3 - [4,5-dimethylthiazol 2-yl] -2,5-diphenyl tetrazolium bromide)) was performed for the evaluation of mitochondrial activity. Statistical analysis for nuclear maturation of oocytes was performed by x2 test. In vitro embryo production, MTT and gene expression were analyzed by unpaired t test. It was observed that BHV-5 did not influence nuclear maturation rate of oocytes or embryonic development, however embryos of group I showed greater mitochondrial viability, and embryos of group II had a decrease in genes expression of Bax and caspase-2, suggesting that the virus inhibited the process of programmed cell death in bovine embryos seven days post-fertilization, in order to promote viral spread / Doutor

Lawsonia intracellularis and the disease it causes in horses, equine proliferative enteropathy (EPE), is an emerging pathogen of increasing importance to the horse industry from both an economic and welfare standpoint. Long recognized as an economically important disease of swine, the hallmark of EPE is a protein-losing enteropathy, where affected horses suffer weight loss and some ultimately succumb to the disease despite aggressive treatment. There are currently no known EPE preventative measures and the epidemiology of the disease remains poorly defined. While EPE is a sporadic disease affecting less than 25% of exposed horses, some farms experience clinical cases year after year. Further, weanlings are uniquely susceptible to this disease, although no conclusive reason for this predisposition has been identified. The overall hypothesis is that the host immune response plays a significant role in the susceptibility of weanlings to L. intracellularis infection and the occurrence of clinical equine proliferative enteropathy. To test this hypothesis, four individual hypotheses were proposed: (H1) previous farm history of EPE does not have an effect on weanling seroprevalence, (H2) passively-acquired antibodies do not have an effect on susceptibility to L. intracellularis and the occurrence of EPE, (H3) the serological status of mares can be used to determine the role they play in the epidemiology of EPE on endemic farms, and (H4) L. intracellularis-specific IFN-g expression is not associated with increased resistance to EPE.

Equine protozoal myeloencephalitis (EPM), caused by the protozoan parasite Sarcocystis neurona, is one of the most important neurological diseases of horses in the Americas. While seroprevalence of S. neurona in horses is high, clinical manifestation of EPM occurs in less than 1% of infected horses. Factors governing the occurrence and severity of EPM are largely unknown, although horse immunity might play an important role in clinical outcome. We hypothesize that EPM occurs due to an aberrant immune response, which will be discernable in the equine IgG subisotypes a, b, and (T) that recognize S. neurona in infected diseased horses versus infected but clinically healthy horses. Based on previously-established serum antibody concentrations for IgG subisotypes in healthy horses, standard curves were generated and served to establish the concentration of antigen-specific IgG subisotypes in equine serum and CSF in infected diseased and infected normal horses. The subisotype concentrations and ratios between subisotypes were analyzed to assess whether neurological disease is associated with detectable differences in the antibody response elicited by infection. Results indicate a type I biased immune response in infected diseased horses, implicating the role of immunity in the development of EPM.

Pituitary pars intermedia dysfunction (PPID) is one of the most common endocrine diseases affecting senior horses. PPID causes abnormally high concentrations of adrenocorticotropic hormone (ACTH) in the plasma and a very distinct, long, shaggy haircoat (hypertrichosis). At present, the recommended treatment for PPID is daily oral administration of pergolide mesylate. Due to the increased ACTH levels associated with PPID, it is commonly thought that these horses are immunosuppressed and at increased risk of opportunistic infections, although current research in this area is sparse. Additionally, it is not well-understood how treatment with Prascend® (pergolide tablets) affects endocrine measures other than ACTH and if it also impacts the immune response. To better understand how PPID influences endocrine and immune function in the horse, Non-PPID horses (n=10), untreated PPID horses (n=9), and PRASCEND-treated PPID horses (n=9) were followed over 15 months. Endocrine measures assessed included basal ACTH, ACTH responses to thyrotropin-releasing hormone (TRH) stimulation tests, basal insulin, insulin responses to oral sugar tests (OST), total cortisol, and free cortisol. Systemic immune function measures included basal and stimulated whole blood and peripheral blood mononuclear cell (PBMCs) cytokine and receptor expression, plasma myeloperoxidase levels, and complete blood counts. Localized immune function measures within the lung included cytokine and receptor expression after stimulation of cells obtained via bronchoalveolar lavage (BAL), myeloperoxidase levels in BAL fluid, and BAL fluid cytology. We hypothesized that PPID would affect immune function, but that any alterations would be corrected by treatment with PRASCEND. Results for the endocrine analyses showed that basal ACTH was reduced in the PRASCEND-treated horses to the levels of the Non-PPID horses, but ACTH in response to TRH stimulation was only reduced in the PRASCEND-treated horses at non-fall timepoints. PPID did not affect basal insulin, insulin responses to OSTs, total cortisol, or free cortisol, and PRASCEND treatment did not appear to have an impact on these measures either. These results suggest that PPID and hyperinsulinemia/insulin dysregulation are distinct endocrine conditions, and that the excess ACTH in horses with PPID is inactive, as it is unable to stimulate a normal cortisol response. In the immune function analyses, PPID horses had decreased expression of interferon gamma (IFNγ) from PBMCs stimulated with Rhodococcus equi and Escherichia coli and increased transforming growth factor beta (TGFβ) expression from the E. coli-stimulated PBMCs. TGFβ was also increased in PPID horses in the unstimulated whole blood samples. These results suggest that PPID horses are unable to mount an appropriate Th1 response, and that the regulatory subset of T-lymphocytes may be contributing to this decreased Th1 response. Results for the localized immune function analyses may indicate altered Th2 responses within the lung of PPID horses, although these results were severely limited by the sample size available for analyses. PRASCEND did not appear to affect immune function as measured in this study. In summary, PRASCEND successfully reduces basal ACTH in PPID horses and remains the best choice for veterinarians in monitoring dosage and response to PRASCEND treatment. Insulin, total cortisol, and free cortisol were not affected by PPID status or PRASCEND treatment in this study. Immune function was altered in horses with PPID, and it is likely that these horses are indeed at increased risk of opportunistic infection. PRASCEND treatment did not correct the differences in immune function in this study. Additional research is needed to further understand which mechanisms are driving the alterations in immune function for horses with PPID.