scholarly journals The Innate Immune Response to Salmonella enterica Serovar Typhimurium by Macrophages Is Dependent on TREM2-DAP12

2008 ◽  
Vol 76 (6) ◽  
pp. 2439-2447 ◽  
Author(s):  
Julia F. Charles ◽  
Mary Beth Humphrey ◽  
Xiaodan Zhao ◽  
Ellen Quarles ◽  
Mary C. Nakamura ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Innate Immune ◽  
Ros Production ◽  
Innate Response ◽  
Innate Defense ◽  
Early Stages ◽  
Serovar Typhimurium ◽  
Important Regulator ◽  
Dependent Pathway

ABSTRACT Macrophage recognition of Salmonella enterica serovar Typhimurium leads to a cascade of signaling events, including the activation of Src family and Syk kinases and the production of reactive oxygen species (ROS), which are critical for host innate defense during early stages of bacterial infection. ROS production depends on the NADPH oxidase, but little is known about the innate immune receptors and proximal adapters that regulate Salmonella-induced ROS. Herein, we demonstrate that serovar Typhimurium induces ROS through a pathway that requires both triggering receptor expressed on myeloid cells 2 (TREM2) and DAP12. This pathway is highly analogous to the pathways utilized by Fc receptors and integrins to regulate ROS production. Oral infection of mice with serovar Typhimurium demonstrates that the DAP12-dependent pathway regulates cecal colonization during early stages of Salmonella infection. Thus, DAP12 is an important regulator of Salmonella-induced ROS production in macrophages, and TREM2 is essential for linking DAP12 to the innate response to serovar Typhimurium.

scholarly journals Flagella and Chemotaxis Are Required for Efficient Induction of Salmonella enterica Serovar Typhimurium Colitis in Streptomycin-Pretreated Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 4138-4150 ◽  
Author(s):  
Bärbel Stecher ◽  
Siegfried Hapfelmeier ◽  
Catherine Müller ◽  
Marcus Kremer ◽  
Thomas Stallmach ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Innate Immune ◽  
Gastrointestinal Infections ◽  
Infection Models ◽  
Serovar Typhimurium ◽  
Efficient Induction ◽  
Toll Like Receptor 5

ABSTRACT Salmonella enterica subspecies 1 serovar Typhimurium is a common cause of gastrointestinal infections. The host's innate immune system and a complex set of Salmonella virulence factors are thought to contribute to enteric disease. The serovar Typhimurium virulence factors have been studied extensively by using tissue culture assays, and bovine infection models have been used to verify the role of these factors in enterocolitis. Streptomycin-pretreated mice provide an alternative animal model to study enteric salmonellosis. In this model, the Salmonella pathogenicity island 1 type III secretion system has a key virulence function. Nothing is known about the role of other virulence factors. We investigated the role of flagella in murine serovar Typhimurium colitis. A nonflagellated serovar Typhimurium mutant (fliGHI) efficiently colonized the intestine but caused little colitis during the early phase of infection (10 and 24 h postinfection). In competition assays with differentially labeled strains, the fliGHI mutant had a reduced capacity to get near the intestinal epithelium, as determined by fluorescence microscopy. A flagellated but nonchemotactic cheY mutant had the same virulence defects as the fliGHI mutant for causing colitis. In competitive infections, both mutants colonized the intestine of streptomycin-pretreated mice by day 1 postinfection but were outcompeted by the wild-type strain by day 3 postinfection. Together, these data demonstrate that flagella are required for efficient colonization and induction of colitis in streptomycin-pretreated mice. This effect is mostly attributable to chemotaxis. Recognition of flagellar subunits (i.e., flagellin) by innate immune receptors (i.e., Toll-like receptor 5) may be less important.

scholarly journals Caspase-1-Mediated Activation of Interleukin-1β (IL-1β) and IL-18 Contributes to Innate Immune Defenses against Salmonella enterica Serovar Typhimurium Infection

2006 ◽  
Vol 74 (8) ◽  
pp. 4922-4926 ◽  
Author(s):  
Bärbel Raupach ◽  
Soo-Kyung Peuschel ◽  
Denise M. Monack ◽  
Arturo Zychlinsky
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Immune Defense ◽  
Innate Immune ◽  
Interleukin 1Β ◽  
Intestinal Phase ◽  
Caspase 1 ◽  
Serovar Typhimurium ◽  
Deficient Mice

ABSTRACTCaspase-1 (Casp-1) mediates the processing of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 to their mature forms. Casp-1-deficient mice succumb more rapidly toSalmonellachallenge than do wild-type animals. Both Casp-1 substrates, IL-18 and IL-1β, are relevant for control ofSalmonella entericaserovar Typhimurium. We used IL-18−/−and IL-1β−/−mice in addition to administration of recombinant IL-18 to Casp-1−/−mice to demonstrate that IL-18 is important for resistance to the systemic infection but not for resistance to the intestinal phase of the infection. This suggests that IL-1β is critical for the intestinal phase of the disease. Thus, we show that Casp-1 is essential for host innate immune defense againstS. entericaserovar Typhimurium and that Casp-1 substrates are required at distinct times and anatomical sites.

scholarly journals Induction of a Novel Chicken Toll-Like Receptor following Salmonella enterica Serovar Typhimurium Infection

2006 ◽  
Vol 74 (3) ◽  
pp. 1692-1698 ◽  
Author(s):  
Rowan Higgs ◽  
Paul Cormican ◽  
Sarah Cahalane ◽  
Brenda Allan ◽  
Andrew T. Lloyd ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Bioinformatic Analysis ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Tlr2 Expression ◽  
Embryonic Fibroblasts ◽  
Serovar Typhimurium

ABSTRACT Toll-like receptors (TLRs) are a group of highly conserved molecules that initiate the innate immune response to pathogens by recognizing structural motifs expressed by microbes. We have identified a novel TLR, TLR15, by bioinformatic analysis of the chicken genome, which is distinct from any known vertebrate TLR and thus appears to be avian specific. The gene for TLR15 was sequenced and is found on chromosome 3, and it has archetypal TIR and transmembrane domains and a distinctive arrangement of extracellular leucine-rich regions. mRNA for TLR15 was detected in the spleen, bursa, and bone marrow of healthy chickens, suggesting a role for this novel receptor in constitutive host defense. Following in vivo Salmonella enterica serovar Typhimurium infection, quantitative real-time PCR demonstrated significant upregulation of TLR15 in the cecum of infected chickens. Interestingly, similar induction of TLR2 expression following infection was also observed. In vitro studies revealed TLR15 upregulation in chicken embryonic fibroblasts stimulated with heat-killed S. enterica serovar Typhimurium. Collectively, these results suggest a role for the TLR in avian defense against bacterial infection. We hypothesize that TLR15 may represent an avian-specific TLR that has been either retained in chicken and lost in other taxa or gained in the chicken.

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