Selective expansion of the monocytic lineage directed by bacterial infection.
CCR2-mediated recruitment of Ly6C(high) monocytes is essential for defense against a range of microbial pathogens. Although our understanding of monocyte trafficking to inflammatory sites is increasing, how innate immune inflammation influences monocyte development and maturation during microbial infection remains undefined. Herein, we demonstrate that infection with the intracellular bacterial pathogen Listeria monocytogenes specifically and selectively promotes monopoiesis. Systemic infection with virulent L. monocytogenes induces marked proliferation of bone marrow monocyte precursors and results in depletion of myeloid progenitors. Proliferation of monocyte precursors correlates with the intensity of systemic infection and is unaffected by the density of monocytes in the bone marrow. Although MyD88/Trif-mediated signaling is not required for early emigration of the mature monocyte population from the bone marrow, replenishment of monocyte populations depends on MyD88/Trif. Our studies demonstrate that TLR-mediated signals play an essential role in the maintenance of monocyte homeostasis during systemic bacterial infection.
Serbina
Natalya V
NV
Infectious Disease Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Immunology Program, Sloan-Kettering Institute, New York, NY 10021, USA.
Hohl
Tobias M
TM
Cherny
Mathew
M
Pamer
Eric G
EG
D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology*; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte; D006706:Homeostasis; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055017:Monocyte-Macrophage Precursor Cells / Q000166:cytology*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D053594:Myeloid Differentiation Factor 88; C470409:TICAM1 protein, human; D051193:Toll-Like Receptors