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Mucosal Immunol. 2019 May;12(3):772-783. doi: 10.1038/s41385-019-0147-3. Epub 2019 Feb 19.

Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis.

Author information

1
Meakins-Christie Laboratories, Department of Medicine, Department of Pathology, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
2
Department of Animal Science, McGill University, Sainte-Ann-de-Bellevue, QC, H9X 3V9, Canada.
3
Meakins-Christie Laboratories, Department of Microbiology and Immunology, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada.
4
McGill International TB Centre, Montreal, QC, H4A 3J1, Canada.
5
Institute of Parasitology, McGill University, Sainte-Ann-de-Bellevue, QC, H9X 3V9, Canada.
6
Meakins-Christie Laboratories, Department of Medicine, Department of Pathology, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada. maziar.divangahi@mcgill.ca.
7
Meakins-Christie Laboratories, Department of Microbiology and Immunology, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada. maziar.divangahi@mcgill.ca.
8
McGill International TB Centre, Montreal, QC, H4A 3J1, Canada. maziar.divangahi@mcgill.ca.
9
Meakins-Christie Laboratories, Department of Medicine, Department of Pathology, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada. irah.king@mcgill.ca.
10
Meakins-Christie Laboratories, Department of Microbiology and Immunology, McGill University Health Centre, Montreal, QC, H4A 3J1, Canada. irah.king@mcgill.ca.

Abstract

Current treatments for tuberculosis (TB) are effective in controlling Mycobacterium tuberculosis (Mtb) growth, yet have significant side effects and do not prevent reinfection. Therefore, it is critical to understand why our host defense system is unable to generate permanent immunity to Mtb despite prolonged anti-tuberculosis therapy (ATT). Here, we demonstrate that treatment of mice with the most widely used anti-TB drugs, rifampicin (RIF) or isoniazid (INH) and pyrazinamide (PYZ), significantly altered the composition of the gut microbiota. Unexpectedly, treatment of mice with the pro-Mtb drugs INH and PYZ, but not RIF, prior to Mtb infection resulted in an increased bacterial burden, an effect that was reversible by fecal transplantation from untreated animals. Mechanistically, susceptibility of INH/PYZ-treated mice was associated with impaired metabolism of alveolar macrophages and defective bactericidal activity. Collectively, these data indicate that dysbiosis induced by ATT administered to millions of individuals worldwide may have adverse effects on the anti-Mtb response of alveolar macrophages.

PMID:
30783183
DOI:
10.1038/s41385-019-0147-3
[Indexed for MEDLINE]

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