Macrophage susceptibility to infection by Ghanaian Mycobacterium tuberculosis complex lineages 4 and 5 varies with self-reported ethnicity.

Autor:	Osei-Wusu S; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.; West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Legon, Ghana., Tetteh JKA; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Musah AB; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Ntiamoah DO; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Arthur N; Department of Chest Diseases, Korle-Bu Teaching Hospital, Accra, Ghana., Adjei A; Department of Chest Diseases, Korle-Bu Teaching Hospital, Accra, Ghana., Arbues A; Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland., Ofori EA; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Mensah KA; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Galevo SEA; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Frempong AF; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Asare P; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Asante-Poku A; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Otchere ID; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Kusi KA; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana., Lenz TL; Research Group for Evolutionary Immunogenomics, Department of Biology, University of Hamburg, Hamburg, Germany., Gagneux S; Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland., Portevin D; Swiss Tropical and Public Health Institute, Allschwil, Switzerland.; University of Basel, Basel, Switzerland., Yeboah-Manu D; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2023 Aug 14; Vol. 13, pp. 1163993. Date of Electronic Publication: 2023 Aug 14 (Print Publication: 2023).
DOI:	10.3389/fcimb.2023.1163993
Abstrakt:	Background: The epidemiology of Mycobacterium tuberculosis complex (MTBC) lineage 5 (L5) infections in Ghana revealed a significantly increased prevalence in Ewes compared to other self-reported ethnic groups. In that context, we sought to investigate the early phase of tuberculosis (TB) infection using ex vivo infection of macrophages derived from the blood of Ewe and Akan ethnic group volunteers with MTBC L4 and L5 strains. Methods: The study participants consisted of 16 controls, among which self-reported Akan and Ewe ethnicity was equally represented, as well as 20 cured TB cases consisting of 11 Akans and 9 Ewes. Peripheral blood mononuclear cells were isolated from both healthy controls and cured TB cases. CD14 + monocytes were isolated and differentiated into monocyte-derived macrophages (MDMs) before infection with L4 or L5 endemic strains. The bacterial load was assessed after 2 hours (uptake) as well as 3 and 7 days post-infection. Results: We observed a higher capacity of MDMs from Ewes to phagocytose L4 strains (p < 0.001), translating into a higher bacillary load on day 7 (p < 0.001) compared to L5, despite the higher replication rate of L5 in Ewe MDMs (fold change: 1.4 vs. 1.2, p = 0.03) among the controls. On the contrary, within macrophages from Akans, we observed a significantly higher phagocytic uptake of L5 (p < 0.001) compared to L4, also translating into a higher load on day 7 (p = 0.04). However, the replication rate of L4 in Akan MDMs was higher than that of L5 (fold change: L4 = 1.2, L4 = 1.1, p = 0.04). Although there was no significant difference in the uptake of L4 and L5 among cured TB cases, there was a higher bacterial load of both L4 (p = 0.02) and L5 (p = 0.02) on day 7 in Ewe MDMs. Conclusion: Our results suggest that host ethnicity (driven by host genetic diversity), MTBC genetic diversity, and individual TB infection history are all acting together to modulate the outcome of macrophage infections by MTBC. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer VF declared a past collaboration with the author SG to the handling editor. (Copyright © 2023 Osei-Wusu, Tetteh, Musah, Ntiamoah, Arthur, Adjei, Arbues, Ofori, Mensah, Galevo, Frempong, Asare, Asante-Poku, Otchere, Kusi, Lenz, Gagneux, Portevin and Yeboah-Manu.)
Databáze:	MEDLINE
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