CD46 accelerates macrophage-mediated host susceptibility to meningococcal sepsis in a murine model
Number of Authors: 5
2017 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 47, no 1, 119-130 p.Article in journal (Refereed) Published
CD46, a membrane cofactor expressed on all nucleated human cells, plays an essential role in suppressing autoimmune reactions and protecting host cells from complement-mediated attack. Human transgenic CD46 homozygousmice (CD46(+/+)) are prone to lethal sepsis upon infection with Neisseria meningitidis (N. meningitidis). However, the underlying mechanisms are poorly understood. Here, we determined thatCD46(+/+) mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro-inflammatory mediators such as IL-6, TNF, IL-12, and IL-1 beta In the presence of M-CSF or GM-CSF, CD46 signaling enhances monocyte-macrophage differentiation. Additionally, CD46(+/+) macrophages rapidly undergo apoptosis upon LPS challenge or meningococcal infection, which could contribute to uncontrolled bacterial dissemination in vivo. Adoptive transfer of CD46(+/+) peritoneal macrophages aggravated septic responses in wild-type mice, but the depletion of macrophages partially alleviated septic reactions in CD46(+/+) mice after N. meningitidis infection. Our findings reveal a novel role of CD46 in accelerating inflammatory responses upon meningococcal infection or LPS stimulation by regulating the functional polarization and survival of macrophages.
Place, publisher, year, edition, pages
2017. Vol. 47, no 1, 119-130 p.
CD46, LPS, Macrophages, Neisseria meningitidis, Sepsis
Biological Sciences Immunology in the medical area
IdentifiersURN: urn:nbn:se:su:diva-141260DOI: 10.1002/eji.201646397ISI: 000394839400016PubMedID: 27794168OAI: oai:DiVA.org:su-141260DiVA: diva2:1088167