Crosstalk between CD64+MHCII+ macrophages and CD4+ T cells drives joint pathology during chikungunya

Crosstalk between CD64+MHCII+ macrophages and CD4+ T cells drives joint pathology during chikungunya

EMBO Molecular Medicine

10.1038/s44321-024-00028-y

http://dx.doi.org/10.1038/s44321-024-00028-y

Fok-Moon Lum, Yi-Hao Chan, Teck-Hui Teo, Etienne Becht, Siti Naqiah Amrun, Karen WW Teng, Siddesh V Hartimath, Nicholas KW Yeo, Wearn-Xin Yee, Nicholas Ang, Anthony M Torres-Ruesta, Siew-Wai Fong, Julian L Goggi, Evan W Newell, Laurent Renia, Guillaume Carissimo, Lisa FP Ng

08 February 2024

Lum, F.-M., Chan, Y.-H., Teo, T.-H., Becht, E., Amrun, S. N., Teng, K. W., Hartimath, S. V., Yeo, N. K., Yee, W.-X., Ang, N., Torres-Ruesta, A. M., Fong, S.-W., Goggi, J. L., Newell, E. W., Renia, L., Carissimo, G., & Ng, L. F. (2024). Crosstalk between CD64+MHCII+ macrophages and CD4+ T cells drives joint pathology during chikungunya. EMBO Molecular Medicine, 16(3), 641–663. https://doi.org/10.1038/s44321-024-00028-y

Communications between immune cells are essential to ensure appropriate coordination of their activities. Here, we observed the infiltration of activated macrophages into the joint-footpads of chikungunya virus (CHIKV)-infected animals. Large numbers of CD64+MHCII+ and CD64+MHCII- macrophages were present in the joint-footpad, preceded by the recruitment of their CD11b+Ly6C+ inflammatory monocyte precursors. Recruitment and differentiation of these myeloid subsets were dependent on CD4+ T cells and GM-CSF. Transcriptomic and gene ontology analyses of CD64+MHCII+ and CD64+MHCII- macrophages revealed 89 differentially expressed genes, including genes involved in T cell proliferation and differentiation pathways. Depletion of phagocytes, including CD64+MHCII+ macrophages, from CHIKV-infected mice reduced disease pathology, demonstrating that these cells play a pro-inflammatory role in CHIKV infection. Together, these results highlight the synergistic dynamics of immune cell crosstalk in driving CHIKV immunopathogenesis. This study provides new insights in the disease mechanism and offers opportunities for development of novel anti-CHIKV therapeutics.

Attribution 4.0 International (CC BY 4.0)

This research is supported by core funding from: Biomedical Research Council, A*STAR Infectious Diseases Labs
Grant Reference no. : NA

This research / project is supported by the National Medical Research Council - Open-Fund Young Investigator Research Grant
Grant Reference no. : OFYIRG22jul-0044, OFYIRG19nov-0051

This research / project is supported by the National Research Foundation - Health and Biomedical Sciences (HBMS) Open Fund Shared Infrastructure Support Grant under the Immunomonitoring Service Platform project
Grant Reference no. : NRF2017_SISFP09

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https://oar.a-star.edu.sg/communities-collections/articles/20829

1757-4684

Infectious Disease Labs

https://www.embopress.org/doi/epdf/10.1038/s44321-024-00028-y