Meningococcal Outer Membrane Protein NhhA Triggers Apoptosis in Macrophages

PLoS One

Hong Sjölinder¹  Georg Altenbacher¹  Matthias Hagner¹  Mikael Sjölinder¹  Sophia Schedin-Weiss²  Wei Sun² 

[1] Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden;Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Centre, Uppsala University, Uppsala, Sweden

关键词: Apoptosis;    Macrophages;    Neisseria meningitidis;    Meningococcal disease;    Nitric oxide;    Cell staining;    Cytokines;    Outer membrane proteins;   

DOI  :  10.1371/journal.pone.0029586

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Phagocytotic cells play a fundamental role in the defense against bacterial pathogens. One mechanism whereby bacteria evade phagocytosis is to produce factors that trigger apoptosis. Here we identify for the first time a meningococcal protein capable of inducing macrophage apoptosis. The conserved meningococcal outer membrane protein NhhA (Neisseria hia/hsf homologue A, also known as Hsf) mediates bacterial adhesion and interacts with extracellular matrix components heparan sulphate and laminin. Meningococci lacking NhhA fail to colonise nasal mucosa in a mouse model of meningococcal disease. We found that exposure of macrophages to NhhA resulted in a highly increased rate of apoptosis that proceeded through caspase activation. Exposure of macrophages to NhhA also led to iNOS induction and nitric oxide production. However, neither nitric oxide production nor TNF-α signaling was found to be a prerequisite for NhhA-induced apoptosis. Macrophages exposed to wildtype NhhA-expressing meningococci were also found to undergo apoptosis whereas NhhA-deficient meningococci had a markedly decreased capacity to induce macrophage apoptosis. These data provide new insights on the role of NhhA in meningococcal disease. NhhA-induced macrophage apoptosis could be a mechanism whereby meningococci evade immunoregulatory and phagocytotic actions of macrophages.

【 授权许可】

CC BY