T cells help to amplify inflammatory responses induced by Salmonella enterica serotype Typhimurium in the intestinal mucosa.
Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the ceca of streptomycin-pretreated mice. We determined global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. The gene expression profile was dominated by T-cell-derived cytokines and genes whose expression is known to be induced by these cytokines. Markedly increased mRNA levels of genes encoding gamma interferon (IFN-gamma), interleukin-22 (IL-22), and IL-17 were detected by quantitative real-time PCR. Furthermore, the mRNA levels of genes whose expression is induced by IFN-gamma, IL-22, or IL-17, including genes encoding macrophage inflammatory protein 2 (MIP-2), inducible nitric oxide synthase (Nos2), lipocalin-2 (Lcn2), MIP-1alpha, MIP-1beta, and keratinocyte-derived cytokine (KC), were also markedly increased. To assess the importance of T cells in orchestrating this proinflammatory gene expression profile, we depleted T cells by using a monoclonal antibody prior to investigating cecal inflammation caused by serotype Typhimurium in streptomycin-pretreated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in gross pathology, a significantly reduced recruitment of neutrophils, and a marked reduction in mRNA levels of Ifn-gamma, Il-22, Il-17, Nos2, Lcn2, and Kc. Our results suggest that T cells play an important role in amplifying inflammatory responses induced by serotype Typhimurium in the cecal mucosa.
Godinez
Ivan
I
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA 95616-8645, USA.
Haneda
Takeshi
T
Raffatellu
Manuela
M
George
Michael D
MD
Paixão
Tatiane A
TA
Rolán
Hortensia G
HG
Santos
Renato L
RL
Dandekar
Satya
S
Tsolis
Renée M
RM
Bäumler
Andreas J
AJ
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D017252:CD3 Complex / Q000276:immunology; D002432:Cecum / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis / Q000235:genetics; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D012486:Salmonella typhimurium / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000209:Acute-Phase Proteins; D017252:CD3 Complex; D016207:Cytokines; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse