1887

Abstract

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.

In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against and and their purified major surface glycoproteins (Msgs).

To study the potential of newly synthesized hFc-CLR fusions on binding to and its Msg.

A library of new synthesized hFc-CLR fusions was screened against and 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.

We detected a number of the CLR hFc-fusions displayed significant binding with and 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 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 (), implicated in recognizing terminal N-acetylgalactosamine (GalNAc) found in the glycoproteins of microbial pathogens was significantly up-regulated during infection.

The data herein add to the growing list of CLRs recognizing and provide insights for further study of organism/host immune cell interactions.

Funding
This study was supported by the:
  • National Heart, Lung, and Blood Institute (Award HL62150)
    • Principle Award Recipient: AndrewH. Limper
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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/content/journal/jmm/10.1099/jmm.0.001470
2021-12-10
2022-01-28
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