Sequential MyD88-independent and -dependent activation of innate immune responses to intracellular bacterial infection.
Microbial infections induce chemokine and cytokine cascades that coordinate innate immune defenses. Infection with the intracellular bacterial pathogen Listeria monocytogenes induces CCR2-dependent monocyte recruitment and activation, an essential response for host survival. Herein we show that invasive L. monocytogenes, but not killed or noninvasive bacteria, induce secretion of MCP-1, the requisite chemokine for monocyte recruitment. Induction of MCP-1, but not TNF or IL-12, following L. monocytogenes infection is MyD88 independent. Consistent with these results, MyD88 deficiency does not impair monocyte recruitment to L. monocytogenes infected spleens, but prevents monocyte activation. Our results indicate that distinct microbial signals activate innate immune responses in an ordered, step-wise fashion, providing a mechanism to specify and modulate antimicrobial effector functions.
Serbina
Natalya V
NV
Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Immunology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10021, USA.
Kuziel
William
W
Flavell
Richard
R
Akira
Shizuo
S
Rollins
Barrett
B
Pamer
Eric G
EG
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology*; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D007113:Immunity, Innate; D008088:Listeriosis / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D018932:Chemokine CCL2; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic