CCR2-mediated recruitment of Ly6Chigh 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.

Aspergillus fumigatus is an environmental fungus that causes life-threatening infections in neutropenic patients. In the absence of intact innate immunity, inhaled A. fumigatus spores (conidia) germinate in the lung, forming hyphae that invade blood vessels and disseminate to other tissues. Although macrophages and neutrophils are postulated to provide defense against invasive fungal infection, animal models and human studies suggest that circulating monocytes also contribute to antifungal immunity. Although human monocyte subsets, defined as either CD14+CD16− or CD14+CD16+, have been extensively characterized, their respective roles during fungal infection remain undefined. We isolated CD14+CD16− and CD14+CD16+ monocytes from healthy allogeneic hematopoietic stem cell transplantation donors and compared their ability to phagocytose and inhibit A. fumigatus conidia. Both monocyte subsets efficiently phagocytose conidia, but only CD14+CD16− monocytes inhibit conidial germination yet secrete little TNF. In contrast CD14+CD16+ do not inhibit conidial germination and secrete large amounts of TNF. Although CD14+CD16− and CD14+CD16+ monocytes differ in their response to dormant conidia, responses are similar if conidia are already germinated at the time of monocyte uptake. Our study demonstrates that functional CD14+CD16− and CD14+CD16+ monocytes can be isolated from allogeneic hematopoietic stem cell transplantation donors and that these subsets differ in their response to A. fumigatus conidia.