No description available.

No description available.

No description available.

No description available.

Herein we describe a novel APC population in mice, designated LAPCs. LAPCs are BM-derived myeloid leukocytes, distinctive from other immune cells. As APCs, LAPCs respond to various virus infections including VACV, CBV3 and influenza A virus. Notably, influenza virus-activated LAPCs capture Ag in the lungs, and migrate into the DLN and spleen with delayed kinetics compared to DCs. In the DLN, influenza virus-activated LAPCs co-localize with T cells and selectively induce Th2 effector cell polarization by cell-cell contact-mediated modulation of GATA-3 expression. In support of a role for LAPCs in anti-influenza T2 immunity, adoptive transfer experiments revealed that influenza virus-activated LAPCs selectively augmented Th2 effector T cell responses in the DLN, increased production of anti-influenza immunoglobulin (Ig) including IgE in peripheral blood and increased levels of IL-5 and eotaxin in BAL fluid in recipient influenza infected mice. LAPC recipient mice exhibited exacerbated pulmonary pathology, with delayed viral clearance and enhanced pulmonary eosinophilia. Collectively, these results highlight the importance of LAPCs as novel immuno-modulators of T2 immunity during influenza A virus infection, which is implicated in both immunoprotection and immunopathology. Subsequently, we examined the immuno-modulatory effect of type-I IFN, specifically IFN-on the immune response against pulmonary influenza virus infection. We have provided evidence that a single dose of IFN- (1×105U) augmented DC migration but inhibited LAPC migration into the DLN. mIFN- treatment skewed the immune balance toward T1 immunity, identified as enhanced T1 effector T cell responses (Th1 and CTL) but diminished T2 effector T cell responses (Th2) in influenza virus infected mice. Finally, IFN- treated mice showed accelerated viral clearance and diminished pulmonary eosinophilia in lung tissue compared to control mice. Taken together, these results suggest that anti-influenza T1 and T2 immunity may be modulated differently by DCs and LAPCs, respectively. Furthermore, these results support the therapeutic potential of type I IFNs, especially IFN-, as an alternative antiviral to control both viral replication and immunopathology induced by influenza A virus infection in humans.

Acinetobacter baumannii is an important nosocomial pathogen, frequently associated with morbidity and mortality in immunocompromised patients due to the immuno-ablative treatments, neutropenia and prolonged hospitalization. The ability of A. baumannii to survive in the healthcare setting makes it a frequent problematic pathogen in cancer centres. Much of the interest in A. baumannii has been attributed to its remarkable rapid acquisition of resistance mechanisms A. baumannii is an excellent example of genetic plasticity, with its ability to acquire and express resistance in plasmids and chromosome particularly to carbapenems The aim of this thesis is to look at the molecular epidemiology and resistance mechanisms of 34 non-duplicate A. baumannii in two cancer centres in Cairo, Egypt. Initial sequencing of the ubiquitous blaOXA-51-like gene revealed a large diversity within the strains, with eight different genes identified: blaOXA-64, blaOXA-65, blaOXA-66, blaOXA-69, blaOXA-71, blaOXA-78, blaOXA-94, blaOXA-89/100. Typing with Pulsed-field Gel Electrophoresis (PFGE) showed an overall similarity at only 28.69% between the isolates, with variation in pattern for isolates with similar blaOXA-51-like genes. Typing with Multilocus Sequence Typing (MLST) identified 6 new Sequence Types: ST408 - ST414, in addition to ST331 and ST108 which have been previously found in other regions of the world. All three OXA-type carbapenemases: blaOXA23, blaOXA40 and blaOXA58, responsible for conferring carbapenem resistance were found in the collection studied. Insertion sequences ISAba1, ISAba2 and ISAba3 have been found to upregulate the expression of blaOXA genes. ISAba1 was found upstream of blaOXA23 in 18 strains in this collection The first report of ISAba2 was identified upstream of a blaOXA-51-like gene in this collection. Additionally, ISAba3 was bracketing the blaOXA58 genes, and two isolates harboured hybrid promoters with IS1006 and IS1008 interrupting the upstream ISAba3 sequence. Resistance to Ceftazidime was mediated by Extended-spectrum β-lactamase (ESBL) genes belonging to PER-like group: blaPER-1, blaPER-7 and the first report of blaPER-3 gene and its genetic environment in A. baumannii. In conclusion, this study shows the diversity exhibited by A. baumannii in Egypt. The various resistance mechanisms illustrate the ability of A. baumannii in acquiring and expressing resistance genes, either on plasmids or in the chromosome. Furthermore, the results indicate an urgent need to strict infection control policies and surveillance of antimicrobial use in Egyptian hospitals.

Class of 2010 Abstract / OBJECTIVES:The main purpose of this study was to review recent and good quality studies of the antimicrobial therapy of for moderate to severe (“limb threatening”) DFI. The analysis of these studies was to conclude with one or two “standard” approach to the routine management of this clinical entity. METHODS: This literature review study consisted of an evaluation of clinical trials that compare two or more active systemic antimicrobial regimens for the treatment of moderate to severe (i.e., “limb-threatening”) diabetic foot infections in human patients. Literature sources were identified primarily from OVID MEDLINE, but also included additional tertiary sources. The primary criteria for the clinical studies were: prospective, controlled, randomized and investigator blinded. Studies had to be published after the year 2003, and be available in full-text in English. RESULTS: Ultimately, only four studies were found that met the criteria for consideration. Trials differed in numerous features. All four studies were sponsored by the manufacturer of one of the comparator drugs. Three of the four were non-inferiority design. Evidence is lacking that any of the suggested regimens are superior. CONCLUSIONS: Instead of meeting our original goal of concluding that one or two regimens could be the “standard” management of DFI, we were limited to commentary on the quality and applicability of the current literature on this clinical entity. Numerous suggestions for improvement in the clinical information provided by DFI studies were offered. We eagerly anticipate the publication of the updated IDSA guideline document on DFI.

One of the major challenges facing clinicians is how to effectively manage excessive host immune response to pathogenic insults resulting in sepsis. This is demonstrated by the fact that despite over half-century research efforts, sepsis and its spectrum of diseases (severe sepsis and septic shock) are still associated with poor clinical outcome. Currently, sepsis is a leading cause of death in intensive care units. The immune system protects the host against pathogens and is therefore armed with an arsenal of deadly ammunitions (including chemicals, cells and proteins) necessary for the elimination of microbes. It is therefore paramount that the immune system must develop mechanisms necessary to prevent destruction of the host it is designed to protect. A good example of such a mechanism is found in the subset of lymphocytes known as regulatory T cells (Tregs). There is unequivocal experimental evidence of the role of Tregs in the maintenance of immune homeostasis and self tolerance and aberrant Treg function has been linked with several inflammatory diseases. Since sepsis is a disease marked by a hyper-inflammatory state, I investigated the possible role of Tregs in dampening sepsis-induced excessive inflammation. Using a murine model of lipopolysaccharide (LPS) infusion and bacterial infection, I show that Tregs are essential for survival during sepsis because their depletion leads to acute death to an otherwise non-lethal dose of LPS. This enhanced susceptibility to LPS following Treg depletion was also observed using live E. coli infection. Next, I probed the mechanism by which Tregs protect against LPS challenge. I found that defective Treg function leads to exaggerated activity of two immune cells – CD4+ effector T cells and neutrophils in response to LPS, leading to severe inflammatory response. Hence, this work successfully illustrates the critical role of Tregs in regulating other immune cells and the catastrophic consequences of defective Treg function during an immune response. Overall, this work highlights the significant role of Tregs in the regulation of bacteria associated inflammatory processes. The findings hold implications for the successful management of sepsis and have potential for use in development of adequate therapeutic intervention for sepsis. / October 2016

Yellow avian plumage is a direct result of carotenoid pigments obtained in a bird’s diet and may act as an indicator for individual health, parasite resistance, and status. This study describes breast feather reflectance of adult Prothonotary Warblers (Protonotaria citrea) (n=169), insectivorous Neotropical migrant passerines, throughout the Ultraviolet (UV) and human visible light spectra and examines the relationship between Haemosporidia (pathogen causing Avian Malaria) infection and feather reflectance (n=41). Reflectance was characterized using a Principle Component Analysis evaluating Intensity, Brightness, Hue, UV Intensity, UV Brightness, and UV Chroma. UV and visible light reflectance was higher in birds sampled earlier in the field season (early clutch) (p=0.0017 and p=0.0743 respectively). There was no relationship between infection and either visible light or hue. However, UV reflectance was lower in infected birds (p=0.0843). This study suggests that UV reflectance is an important indicator for the infection status of a Neotropical migrant passerine.

Twelve isolates of Ichthyophthirius multifiliis were successfully established and maintained by serial passage through naïve carp, for a maximum of 39 laboratory cycles. The management system employed was such that large numbers of the parasite were available for all investigations. The ability to induce exit of immature trophonts through media incubation was used to confirm events in the initial stages of host colonisation. The normal course of primary infection was also established providing useful criteria for assessing success of the in vitro systems tested. Survival of both theronts and tomonts within selected monophasic media was investigated. Theronts in Eagles Minimum Essential medium (EMEM), survived and were viable for 120 hours, 72 hours longer than water controls. No further development of the theronts was observed. Tomonts also demonstrated an increased survival time in comparison to the controls with tomites surviving within the cyst for 22 days within EMEM-S media diluted 50:50 with sterile distilled water. Division of tomonts was identified as being precystic, post divisional cystic or cystic, and the frequency of such divisions was dependent upon dilution of media. Sterile viable theronts were recovered at 168h from tomonts that had been incubated within EMEM diluted 30:70 with distilled water. Delayed encystment was achieved by incubation in concentrated media, theront production being delayed for 96h, 72h later than seen in the aquatic environment. Cultured cell monolayers were used as associates within culture systems. Behaviour of theronts on introduction into the culture systems indicated recognition of the cultured tissue as potential host material, sustained contact of up to l20hours was observed between the introduced parasite and cells. However, no developmental markers were identified within the cultured parasite and no significant growth was achieved. Attempts to simulate the situation in vivo by use of multilayered systems and crude cell explants were also unsuccessful. Transmission electron microscopy of the parasite within a cell aggregate system was undertaken at daily intervals up to 120h providing evidence that the parasite was attempting to gain nutrients by phagocytosis. However, increased vacuolation of the parasite during the period of culture was clearly evident leading eventually to parasite death. The significance of the results is discussed in relation to the normal course of infection and the future promise of a long term culture method for this important pathogen.