PMID- 34889727 OWN - NLM STAT- MEDLINE DCOM- 20221229 LR - 20221229 IS - 1473-5644 (Electronic) IS - 0022-2615 (Print) IS - 0022-2615 (Linking) VI - 70 IP - 12 DP - 2021 Dec TI - Additional C-type lectin receptors mediate interactions with Pneumocystis organisms and major surface glycoprotein. LID - 10.1099/jmm.0.001470 [doi] LID - 001470 AB - Introduction. Pathogen-associated molecular patterns' (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with micro-organisms via their carbohydrate recognition domains (CRDs) and engage signalling pathways within the cell resulting in pro-inflammatory and microbicidal responses.Gap statement. In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against Pneumocystis murina and Pneumocystis carinii and their purified major surface glycoproteins (Msgs).Aim. To study the potential of newly synthesized hFc-CLR fusions on binding to Pneumocystis and its Msg.Methods. A library of new synthesized hFc-CLR fusions was screened against Pneumocystis murina and Pneumocystis carinii organisms and their purified major surface glycoproteins (Msgs) found on the respective fungi via modified ELISA. Immunofluorescence assay (IFA) was implemented and quantified to verify results. mRNA expression analysis by quantitative PCR (q-PCR) was employed to detect respective CLRs found to bind fungal organisms in the ELISA and determine their expression levels in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model.Results. We detected a number of the CLR hFc-fusions displayed significant binding with P. murina and P. carinii organisms, and similarly to their respective Msgs. Significant organism and Msg binding was observed for CLR members C-type lectin domain family 12 member A (CLEC12A), Langerin, macrophage galactose-type lectin-1 (MGL-1), and specific intracellular adhesion molecule-3 grabbing non-integrin homologue-related 3 (SIGNR3). Immunofluorescence assay (IFA) with the respective CLR hFc-fusions against whole P. murina life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of the respective CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that macrophage galactose type C-type lectin (Mgl-1), implicated in recognizing terminal N-acetylgalactosamine (GalNAc) found in the glycoproteins of microbial pathogens was significantly up-regulated during infection.Conclusion. The data herein add to the growing list of CLRs recognizing Pneumocystis and provide insights for further study of organism/host immune cell interactions. FAU - Kottom, Theodore J AU - Kottom TJ AD - Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Carmona, Eva M AU - Carmona EM AD - Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Schaefbauer, Kyle AU - Schaefbauer K AD - Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN, USA. FAU - Limper, Andrew H AU - Limper AH AD - Thoracic Diseases Research Unit, Departments of Medicine and Biochemistry, Mayo Clinic College of Medicine, Rochester, MN, USA. LA - eng GR - R01 HL062150/HL/NHLBI NIH HHS/United States PT - Journal Article PL - England TA - J Med Microbiol JT - Journal of medical microbiology JID - 0224131 RN - 0 (Fungal Proteins) RN - X2RN3Q8DNE (Galactose) RN - 0 (Lectins, C-Type) RN - 0 (Membrane Glycoproteins) RN - 0 (RNA, Messenger) RN - Pneumocystis murina SB - IM MH - Animals MH - Mice MH - Fungal Proteins MH - Galactose MH - Host-Pathogen Interactions MH - *Lectins, C-Type/genetics MH - *Membrane Glycoproteins MH - *Pneumocystis/genetics MH - Pneumocystis carinii/genetics MH - *Pneumonia, Pneumocystis/immunology MH - RNA, Messenger PMC - PMC8744274 OTO - NOTNLM OT - C-type lectin receptors (CLRs) OT - carbohydrate recognition domains (CRDs) OT - major surface glycoprotein (Msg) OT - pneumocystis COIS- The authors declare that there are no conflicts of interest. EDAT- 2021/12/11 06:00 MHDA- 2021/12/30 06:00 PMCR- 2021/12/10 CRDT- 2021/12/10 12:15 PHST- 2021/12/10 12:15 [entrez] PHST- 2021/12/11 06:00 [pubmed] PHST- 2021/12/30 06:00 [medline] PHST- 2021/12/10 00:00 [pmc-release] AID - 001470 [pii] AID - 10.1099/jmm.0.001470 [doi] PST - ppublish SO - J Med Microbiol. 2021 Dec;70(12):001470. doi: 10.1099/jmm.0.001470.