| First Author | Pasquevich KA | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 10 | Pages | 2821-33 |
| PubMed ID | 26138432 | Mgi Jnum | J:233063 |
| Mgi Id | MGI:5780661 | Doi | 10.1002/eji.201545530 |
| Citation | Pasquevich KA, et al. (2015) Innate immune system favors emergency monopoiesis at the expense of DC-differentiation to control systemic bacterial infection in mice. Eur J Immunol 45(10):2821-33 |
| abstractText | 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-gamma-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. |
