Host-pathogen Interactions in Ocular and Lung Infection

Download or read book Host-pathogen Interactions in Ocular and Lung Infection written by and published by . This book was released on 2014 with total page 386 pages. Available in PDF, EPUB and Kindle. Book excerpt: The onset of microbial infection triggers a complex series of interactions between the host and the pathogen via the innate immune system. There has been a significant increase in the number of infections caused by multi-drug resistant (MDR) microbes, due to the increased prevalence of such strains. To understand the impact of virulence properties of MDR microbes on the pathogenicity of disease, we assessed the characteristics of MDR ocular isolates of Acinetobacter baumannii. We observed that A. baumannii isolates bear multiple plasmids, are able to adhere to, and invade, human corneal epithelial cells, and form biofilms. We further tested the role of these virulence properties in causing endophthalmitis in a mouse model. We administered intravitreal injections of A. baumannii into the eyes of C57BL/6 mice and monitored disease progression by ophthalmoscopic examination, histological analysis, retina functional analysis, and retinal cell death. Our results demonstrate that MDR A. baumannii isolates causes severe endophthalmitis, resulting in the production of proinflammatory cytokines, neutrophil infiltration, and retinal cell death. We further investigated the role of the retinal pigment epithelium (RPE) in the induction of innate immune responses in C. albicans endophthalmitis. The RPE is thought to play a key role in retinal innate defense. We hypothesized that Toll like receptors (TLRs) mediate innate immune response in C. albicans infection. Our results suggest that TLR-2 initiates the innate immune response, resulting in the production of pro-inflammatory cytokines and anti-microbial peptides (AMPs). Diabetes is strongly associated with a higher rate of mortality in pneumonia infections. We attempted to understand the immune response to infection with MDR Klebiella pneumoniae in vitro using bronchial epithelial cells in both normal and diabetic conditions. We observed elevated levels of IL-6 and IL-8, as well as higher secretion of AMPs in diabetic conditions. We conclude that K. pneumoniae infection further increases inflammation in diabetes beyond what is normally present and that this in turn increases the severity of infection. Taken together, our data indicated that the innate immune system can be both beneficial and detrimental and tight regulation is required to protect the host from excessive inflammation, which damages cells and tissues.