Analysis of genetic variation in the bovine Mannose Receptor gene (MRC1), its influence on receptor expression, and a potential association with resistance to bovine tuberculosis

Holder, A.; Kolakowski, J. F.; Usher, E.; Tzelos, T.; Connelley, T. k.; Shabbir, M. Z.; Gibson, A. J.; Harris, H.; Villarreal-Ramos, B.; Werling, D.

doi:10.64898/2026.06.27.734952

bioRxiv · 10.64898/2026.06.27.734952

Analysis of genetic variation in the bovine Mannose Receptor gene (MRC1), its influence on receptor expression, and a potential association with resistance to bovine tuberculosis

Holder, A.·Kolakowski, J. F.·Usher, E.·Tzelos, T.·Connelley, T. k.·Shabbir, M. Z.·Gibson, A. J.·Harris, H.·Villarreal-Ramos, B.·Werling, D.

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Abstract

Naturally occurring variation in the bovine mannose receptor C-type 1 gene (MRC1) may shape macrophage responses to Mycobacterium (M.) bovis, a key driver of bovine tuberculosis (bTB). We identified four coding region SNPs in MRC1 across Bos taurus (Holstein Friesian, Brown Swiss) and Bos indicus (Boran, Sahiwal) cattle breeds, including a non-synonymous variant, rs380943118 (c.2963G>A; Ser988Asn) in C-type lectin-like domain (CTLD) 6, most prevalent in Sahiwal cattle. Structural modelling suggested that the S988N substitution, which is spatially separated from the monosaccharide binding site of CTLD4, might indirectly affect glycan binding, perhaps through a conformational change in the receptor. Monocyte-derived macrophages upregulated MR expression during differentiation, with heterozygous (G/A) animals showing higher MR expression and increased uptake of GFP-M. bovis BCG, although differences were not statistically significant. Anti-CD206 blockade did not inhibit BCG internalization, either indicating that this specific antibody did not bind to a CTLD involved in ligand binding or that MR is not the sole entry receptor. These results highlight naturally occurring MRC1 polymorphisms that may influence MR structure and macrophage function, providing a foundation for future studies to assess their role in bTB susceptibility. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/734952v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1bffc22org.highwire.dtl.DTLVardef@1422f8aorg.highwire.dtl.DTLVardef@3f3de1org.highwire.dtl.DTLVardef@1f7b960_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Holder, A., Kolakowski, J. F., Usher, E., Tzelos, T., Connelley, T. k., Shabbir, M. Z., Gibson, A. J., Harris, H., Villarreal-Ramos, B., Werling, D.. 2026-07-03. Analysis of genetic variation in the bovine Mannose Receptor gene (MRC1), its influence on receptor expression, and a potential association with resistance to bovine tuberculosis. https://doi.org/10.64898/2026.06.27.734952

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