Monocyte and neutrophil recruitment during oral Salmonella infection is driven by MyD88-derived chemokines.
Oral Salmonella infection recruits phagocytes to Peyer's patches (PP) and MLN. The chemokines induced in infected PP and MLN, the cellular sources during infection and the TLR signaling pathways involved in vivo are not known. Here, we show that CCL2, CXCL9 and CXCL2 mRNA are up-regulated in PP and MLN coincident with the first arrival of monocytes and neutrophils. Laser capture microdissection microscopy revealed that chemokine mRNA up-regulation was differently distributed in PP. Despite this, recruited monocytes and neutrophils formed inflammatory cell clusters throughout PP. Monocytes and neutrophils purified from infected mice preferentially produced CXCL2 and small amounts of CCL2, and neutrophils from infected mice migrated towards CXCL2 and CCL3. Furthermore, phagocyte recruitment to PP and MLN was intact in mice lacking TLR4 alone and when signaling through TLR4 and TLR5 was simultaneously absent; however, recruitment was compromised in MyD88(-/-) and more so in MyD88(-/-)TLR4(-/-) double knockout mice. Phagocyte release into the blood, however, was only marginally reduced in MyD88(-/-)TLR4(-/-) mice. Defective phagocyte recruitment to PP and MLN of MyD88(-/-)TLR4(-/-) mice was paralleled by low chemokine induction. These data provide insight into the chemokines and TLR signaling pathways that orchestrate the early phagocyte response to oral Salmonella infection.
Department of Microbiology and Immunology, Göteborg University, Göteborg, Sweden.
Anna
A
Rydström
Mary Jo
MJ
Wick
D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology; D054426:Chemokine CXCL2 / Q000276:immunology; D054370:Chemokine CXCL9 / Q000276:immunology; D018925:Chemokines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007834:Lasers; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D042282:Microdissection; D009000:Monocytes / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D010581:Peyer's Patches / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012481:Salmonella Infections, Animal / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D054370:Chemokine CXCL9; D018925:Chemokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors