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The Interaction of Pneumocystis with the C-Type Lectin Receptor Mincle Exerts a Significant Role in Host Defense against Infection
| Content Provider | Scilit |
|---|---|
| Author | Kottom, Theodore J. Hebrink, Deanne M. Jenson, Paige E. Nandakumar, Vijayalakshmi Wüthrich, Marcel Wang, Huafeng Klein, Bruce Yamasaki, Sho Lepenies, Bernd Limper, Andrew H. |
| Copyright Year | 2017 |
| Description | 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 FcRγ-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. |
| Ending Page | 3525 |
| Page Count | 11 |
| Starting Page | 3515 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1600744 |
| Journal | The Journal of Immunology |
| Issue Number | 9 |
| Volume Number | 198 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2017-05-01 |
| Access Restriction | Open |
| Subject Keyword | Infectious Diseases Type Lectin Receptor Lectin Receptors Significant Role Defense Against Infection |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
