Neutrophils exert a suppressive effect on Th1 responses to intracellular pathogen Brucella abortus

PLoS Pathog. 2013 Feb;9(2):e1003167. doi: 10.1371/journal.ppat.1003167. Epub 2013 Feb 14.

Abstract

Polymorphonuclear neutrophils (PMNs) are the first line of defense against microbial pathogens. In addition to their role in innate immunity, PMNs may also regulate events related to adaptive immunity. To investigate the influence of PMNs in the immune response during chronic bacterial infections, we explored the course of brucellosis in antibody PMN-depleted C57BL/6 mice and in neutropenic mutant Genista mouse model. We demonstrate that at later times of infection, Brucella abortus is killed more efficiently in the absence of PMNs than in their presence. The higher bacterial removal was concomitant to the: i) comparatively reduced spleen swelling; ii) augmented infiltration of epithelioid histiocytes corresponding to macrophages/dendritic cells (DCs); iii) higher recruitment of monocytes and monocyte/DCs phenotype; iv) significant activation of B and T lymphocytes, and v) increased levels of INF-γ and negligible levels of IL4 indicating a balance of Th1 over Th2 response. These results reveal that PMNs have an unexpected influence in dampening the immune response against intracellular Brucella infection and strengthen the notion that PMNs actively participate in regulatory circuits shaping both innate and adaptive immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Brucella abortus / pathogenicity*
  • Brucellosis / immunology*
  • Brucellosis / virology
  • Cytokines / metabolism
  • Flow Cytometry
  • Immunity, Innate / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Neutrophils / virology
  • Th1 Cells / immunology*
  • Th1 Cells / virology

Substances

  • Cytokines

Grants and funding

This work was funded by the following grants: Centre National de la Recherche Scientifique and Institut National de la Santé et de la Recherche Médicale, France. AM was a recipient of the Foundation de la Recherche Médicale, FRM, France. MICIT/CONICIT (FI-487-09), FIDA-2006-UNA, UCR-Subdivision of Research, FS-CONARE-UNA/UCR/ITCR, NeTropica 8-N-2008, European Communities (MASTERSWITCH projects). This work was done as part of the UCR/DAAD Humboldt Fellow award 2012 to EM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.