Genotype and Th2 cells control monocyte to tissue resident macrophage differentiation during nematode infection of the pleural cavity

Finlay, C. M.; Parkinson, J.; Chan, B. H.; Ajendra, J.; Chenery, A.; Morrison, A.; Houlder, E. L.; Baker, S. M.; Dickie, B.; Boon, L.; MacDonald, A. S.; Konkel, J. E.; Rückerl, D.; Allen, J. E.

doi:10.1101/2021.12.17.472661

bioRxiv · 10.1101/2021.12.17.472661

Genotype and Th2 cells control monocyte to tissue resident macrophage differentiation during nematode infection of the pleural cavity

Finlay, C. M.·Parkinson, J.·Chan, B. H.·Ajendra, J.·Chenery, A.·Morrison, A.·Houlder, E. L.·Baker, S. M.·Dickie, B.·Boon, L.·MacDonald, A. S.·Konkel, J. E.·Rückerl, D.·Allen, J. E.

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Abstract

The recent revolution in tissue-resident macrophage biology has resulted largely from murine studies performed in the C57BL/6 strain. Here, we provide a comprehensive analysis of immune cells in the pleural cavity using both C57BL/6 and BALB/c mice. Unlike C57BL/6 mice, naive tissue-resident Large Cavity Macrophages (LCM) of BALB/c mice failed to fully implement the tissue residency program. Following infection with a pleural-dwelling nematode these pre-existing differences were accentuated with LCM expansion occurring in C57BL/6 but not BALB/c mice. While infection drove monocyte recruitment in both strains, only in C57BL/6 mice were monocytes able to efficiently integrate into the resident pool. Monocyte to macrophage conversion required both T cells and IL-4R signalling. Host genetics are therefore a key influence on tissue resident macrophage biology, and during nematode infection Th2 cells control the differentiation pathway of tissue resident macrophages. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/472661v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@bba5e1org.highwire.dtl.DTLVardef@1876aa4org.highwire.dtl.DTLVardef@16a6b1corg.highwire.dtl.DTLVardef@19e18b6_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Finlay, C. M., Parkinson, J., Chan, B. H., Ajendra, J., Chenery, A., Morrison, A., Houlder, E. L., Baker, S. M., Dickie, B., Boon, L., MacDonald, A. S., Konkel, J. E., Rückerl, D., Allen, J. E.. 2021-12-19. Genotype and Th2 cells control monocyte to tissue resident macrophage differentiation during nematode infection of the pleural cavity. https://doi.org/10.1101/2021.12.17.472661

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