Innate immune system favors emergency monopoiesis at the expense of DC-differentiation to control systemic bacterial infection in mic

KARINA A. PASQUEVICH; KRISTIN BIEBER; MANINA GÜNTER; MATTHIAS GRAUER; OLIVER PÖTZ; ULRIKE SCHLEICHER; TILO BIEDERMANN; SANDRA BEER-HAMMER; HANS-JÖRG BÜHRING; HANS-GEORG RAMMENSEE; LARS ZENDER; INGO B. AUTENRIETH; CLAUDIA LENGERKE; STELLA E. AUTENRIETH

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2015 vol. 45 p. 2821 - 2833

0014-2980

DCs are professional APCs playing a crucial role in the initiation of T-cell responses to combat infection. However, systemic bacterial infection with various pathogens leads to DC-depletion in humans and mice. The mechanisms of pathogen-induced DC-depletion remain poorly understood. Previously, we showed that mice infected with Yersinia enterocolitica (Ye) had impaired de novo DC-development, one reason for DC-depletion. Here, we extend these studies to gain insight into the molecular mechanisms of DC-depletion and the impact of different bacteria on DC-development. We show that the number of bone marrow (BM) hematopoietic progenitors committed to the DC lineage is reduced following systemic infection with different Gram-positive and Gram-negative bacteria. This is associated with a TLR4- and IFN-γ−signaling dependent increase of committed monocyte progenitors in the BM and mature monocytes in the spleen upon Ye-infection. Adoptive transfer experiments revealed that infection-induced monopoiesis occurs at the expense of DC-development. Our data provide evidence for a general response of hematopoietic progenitors upon systemic bacterial infections to enhance monocyte production, thereby increasing the availability of innate immune cells for pathogen control, whereas impaired DC-development leads to DC-depletion, possibly driving transient immunosuppression in bacterial sepsis.