The interaction of pneumocystis with the c-Type lectin receptor mincle exerts a significant role in host defense against infection

Theodore J. Kottom, Deanne M. Hebrink, Paige E. Jenson, Vijayalakshmi Nandakumar, Marcel Wuthrich, Huafeng Wang, Bruce Klein, Sho Yamasaki, Bernd Lepenies, Andrew H. Limper

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of macrophage-inducible C-Type lectin (Mincle) for host defense against Pneumocystis. Binding assays implementing soluble Mincle carbohydrate recognition domain fusion proteins demonstrated binding to intact Pneumocystis carinii as well as to organism homogenates, and they purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with PCP expressed increased Mincle mRNA levels. Mouse macrophages overexpressing Mincle displayed increased binding to P. carinii life forms and enhanced protein tyrosine phosphorylation. The binding of P. carinii to Mincle resulted in activation of FcRg-mediated cell signaling. RNA silencing of Mincle in mouse macrophages resulted in decreased activation of Syk kinase after P. carinii challenge, critical in downstream inflammatory signaling. Mincle-deficient CD4-depleted (Mincle-/-) mice showed a significant defect in organism clearance from the lungs with higher organism burdens and altered lung cytokine responses during Pneumocystis murina pneumonia. Interestingly, Mincle-/- mice did not demonstrate worsened survival during PCP compared with wild-Type mice, despite the markedly increased organism burdens. This may be related to increased expression of anti-inflammatory factors such as IL-1Ra during infection in the Mincle-/- mice. Of note, the P. murina-infected Mincle-/- mice demonstrated increased expression of known C-Type lectin receptors Dectin-1, Dectin-2, and MCL compared with infected wild-Type mice. Taken together, these data support a significant role for Mincle in Pneumocystis modulating host defense during infection.

Original languageEnglish (US)
Pages (from-to)3515-3525
Number of pages11
JournalJournal of Immunology
Issue number9
StatePublished - May 1 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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