Resistance of the brain to Escherichia coli K1 infection depends on MyD88 signaling and the contribution of neutrophils and monocytes.

Abstract

Escherichia coli is the leading cause of Gram-negative neonatal bacterial meningitis and also causes meningitis and meningoencephalitis in older and immunocompromised patients. Here, we determined the contribution of granulocytes, monocytes, and TLR signaling cascades in the resistance of adult mice to Escherichia coli K1 brain infection. Deficiency in MyD88 (myd88(-/-)) but not in TRIF (trif(lps2)) adaptor proteins dramatically reduced the survival of animals. Depletion of CD11b(+) Ly-6G(+) Ly-6C(int) neutrophils by application of the anti-Ly-6G (1A8) monoclonal antibody (MAb) led to higher bacterial loads in cerebellum and spleen tissue and resulted in increased mortality compared to those of isotype-treated controls. Depletion of CD11b(+) Ly-6G(+) Ly-6C(int) neutrophils and CD11b(+) Ly-6G(-) Ly-6C(high) monocytes by administration of the anti-Gr-1 (RB6-8C5) MAb rendered mice even more susceptible to the infection, with higher central nervous system (CNS) and spleen bacterial burdens than anti-Ly-6G-treated animals. Depletion of ∼50% of CD11b(+) Ly-6G(-) Ly-6C(high) monocytes by injection of the anti-CCR2 (MC-21) MAb resulted in a trend toward higher mortality compared to that with isotype treatment. Production of interleukin 1β (IL-1β), IL-6, KC, and MIP-2 in the CNS strongly depended on the bacterial load: increased levels of these cytokines/chemokines were found after depletion of CD11b(+) Ly-6G(+) Ly-6C(int) neutrophils alone or together with CD11b(+) Ly-6G(-) Ly-6C(high) monocytes. These findings identify Toll-like receptor (TLR)-MyD88 signaling and neutrophil and monocyte activity as critical elements in the early host defense against E. coli meningitis.

DOI: 10.1128/IAI.01349-12

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@article{Ribes2013ResistanceOT, title={Resistance of the brain to Escherichia coli K1 infection depends on MyD88 signaling and the contribution of neutrophils and monocytes.}, author={Sandra Ribes and Tommy Regen and Tanja Meister and S Tauber and Sandra Sch{\"{u}tze and Alexander Mildner and Matthias Mack and U K Hanisch and Roland Nau}, journal={Infection and immunity}, year={2013}, volume={81 5}, pages={1810-9} }