Immune Homeostatic Macrophages Programmed by the Bacterial Surface Protein NhhA Potentiate Nasopharyngeal Carriage of Neisseria meningitidis
2016 (English)In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 7, no 1, e01670-15Article in journal (Refereed) Published
Neisseria meningitidis colonizes the nasopharyngeal mucosa of healthy populations asymptomatically although the bacterial surface is rich in motifs that activate the host innate immunity. What determines the tolerant host response to this bacterium in asymptomatic carriers is poorly understood. We demonstrated that the conserved meningococcal surface protein, NhhA, orchestrates monocyte (Mo) differentiation specifically into macrophage-like cells with a CD200Rhi phenotype (NhhA-MΦ). In response to meningococcal stimulation, NhhA-MΦ failed to produce proinflammatory mediators. Instead, they upregulated IL-10 and Th2/Treg-attracting chemokines, such as CCL-17, CCL-18, and CCL-22. Moreover, NhhA-MΦ cells were highly efficient in eliminating bacteria. The in vivo validity of these findings was corroborated using a murine model challenged with N. meningitidis systematically or intranasally. NhhA-modulated immune response protected mice from septic shock; Mo/MΦ depletion abolished this protective effect. Intranasal administration of NhhA induced an anti-inflammatory response, which was associated with N. meningitidis persistence at the nasopharynx. In vitro studies demonstrated that NhhA-triggered Mo differentiation occurred upon engaged toll-like receptor (TLR)1/TLR2 signaling and ERK and JNK activation and required endogenously produced IL-10 and TNF-α. Our findings reveal a strategy that might be adopted by N. meningitidis to maintain asymptomatic nasopharyngeal colonization.
Place, publisher, year, edition, pages
2016. Vol. 7, no 1, e01670-15
Research subject Molecular Genetics
IdentifiersURN: urn:nbn:se:su:diva-129123DOI: 10.1128/mBio.01670-15ISI: 000373933100067OAI: oai:DiVA.org:su-129123DiVA: diva2:919750