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CD46 accelerates ma...
CD46 accelerates macrophage-mediated host susceptibility to meningococcal sepsis in a murine model
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- Wang, Xiao (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Zhang, Ding (författare)
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- Sjölinder, Mikael (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Wan, Yi (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
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- Sjölinder, Hong (författare)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Mälar Hospital, Sweden
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(creator_code:org_t)
- 2016-12-21
- 2017
- Engelska.
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 47:1, s. 119-130
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- CD46
- LPS
- Macrophages
- Neisseria meningitidis
- Sepsis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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