Differentially Evolved Genes of Salmonella Pathogenicity Islands: Insights into the Mechanism of Host Specificity in Salmonella

BACKGROUND: The species Salmonella enterica (S. enterica) includes many serovars that cause disease in avian and mammalian hosts. These serovars differ greatly in their host range and their degree of host adaptation. The host specificity of S. enterica serovars appears to be a complex phenomenon governed by multiple factors acting at different stages of the infection process, which makes identification of the cause/s of host specificity solely by experimental methods difficult. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have employed a molecular evolution and phylogenetics based approach to identify genes that might play important roles in conferring host specificity to different serovars of S. enterica. These genes are 'differentially evolved' in different S. enterica serovars. This list of 'differentially evolved' genes includes genes that encode translocon proteins (SipD, SseC and SseD) of both Salmonella pathogenicity islands 1 and 2 encoded type three secretion systems, sptP, which encodes an effector protein that inhibits the mitogen-activated protein kinase pathway of the host cell, and genes which encode effector proteins (SseF and SifA) that are important in placing the Salmonella-containing vacuole in a juxtanuclear position. CONCLUSIONS/SIGNIFICANCE: Analysis of known functions of these 'differentially evolved genes' indicates that the products of these genes directly interact with the host cell and manipulate its functions and thereby confer host specificity, at least in part, to different serovars of S. enterica that are considered in this study

Interleukin-1 Receptor-Associated Kinase M-Deficient Mice Demonstrate an Improved Host Defense during Gram-negative Pneumonia

Contains fulltext : 108394.pdf (publisher's version ) (Open Access)Pneumonia is a common cause of morbidity and mortality and the most frequent source of sepsis. Bacteria that try to invade normally sterile body sites are recognized by innate immune cells through pattern recognition receptors, among which toll-like receptors (TLRs) feature prominently. Interleukin-1 receptor (IL-1R)-associated kinase (IRAK)-M is a proximal inhibitor of TLR signaling expressed by epithelial cells and macrophages in the lung. To determine the role of IRAK-M in host defense against bacterial pneumonia, IRAK-M-deficient (IRAK-M(-/-)) and normal wild-type (WT) mice were infected intranasally with Klebsiella pneumoniae. IRAK-M mRNA was upregulated in lungs of WT mice with Klebsiella pneumonia, and the absence of IRAK-M resulted in a strongly improved host defense as reflected by reduced bacterial growth in the lungs, diminished dissemination to distant body sites, less peripheral tissue injury and better survival rates. Although IRAK-M(-/-) alveolar macrophages displayed enhanced responsiveness toward intact K. pneumoniae and Klebsiella lipopolysaccharide (LPS) in vitro, IRAK-M(-/-) mice did not show increased cytokine or chemokine levels in their lungs after infection in vivo. The extent of lung inflammation was increased in IRAK-M(-/-) mice shortly after K. pneumoniae infection, as determined by semiquantitative scoring of specific components of the inflammatory response in lung tissue slides. These data indicate that IRAK-M impairs host defense during pneumonia caused by a common gram-negative respiratory pathogen

The role of eye-associated lymphoid tissue in corneal immune protection

Because the cornea is optimized for refraction, it relies on supporting tissues for moistening and nutrition and in particular for immune protection. Its main support tissue is the conjunctiva, in addition to the lacrimal gland, the latter which provides soluble mediators via the tear film. The cornea and conjunctiva constitute a moist mucosal surface and there is increasing evidence that apart from innate defence mechanisms, also lymphoid cells contribute to the normal homeostasis of the corneal surface. A Medline-based literature search was performed in order to review the existing literature on the existence, composition and functions of mucosa-associated lymphoid tissue (MALT) at the ocular surface for corneal protection. The existence of lymphoid cells at the ocular surface and appendage has been known for many years, but for a long time they were believed erroneously to be inflammatory cells. More recent research has shown that in addition to the known presence of lymphoid cells in the lacrimal gland, they also form MALT in the conjunctiva as conjunctiva-associated lymphoid tissue (CALT) and in the lacrimal drainage system as lacrimal drainage-associated lymphoid tissue (LDALT). Together this constitutes an eye-associated lymphoid tissue (EALT), which is a new component of the mucosal immune system of the body. When the topographical distribution of CALT is projected onto the ocular surface, it overlies the cornea during eye closure and is hence in a suitable position to assist the corneal immune protection during blinking and overnight. It can detect corneal antigens and prime respective effector cells, or distribute protective factors as secretory IgA