Translocated microbiome composition determines immunological outcome in treated HIV infection

Nganou-Makamdop K, Talla A, Sharma AA, Darko S, Ransier A, Laboune F, Chipman JG, Beilman GJ, Hoskuldsson T, Fourati S, Schmidt TE, Arumugam S, Lima NS, Moon D, Callisto S, Schoephoerster J, Tomalka J, Mugyenyi P, Ssali F, Muloma P, Ssengendo P, Leda AR, Cheu RK, Flynn JK, Morou A, Brunet-Ratnasingham E, Rodriguez B, Lederman MM, Kaufmann DE, Klatt NR, Kityo C, Brenchley JM, Schacker TW, Sekaly RP, Douek DC (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cell Elsevier

Book Volume: 184

Pages Range: 3899-3914.e16

Journal Issue: 15

DOI: 10.1016/j.cell.2021.05.023

Abstract

The impact of the microbiome on HIV disease is widely acknowledged although the mechanisms downstream of fluctuations in microbial composition remain speculative. We detected rapid, dynamic changes in translocated microbial constituents during two years after cART initiation. An unbiased systems biology approach revealed two distinct pathways driven by changes in the abundance ratio of Serratia to other bacterial genera. Increased CD4 T cell numbers over the first year were associated with high Serratia abundance, pro-inflammatory innate cytokines, and metabolites that drive Th17 gene expression signatures and restoration of mucosal integrity. Subsequently, decreased Serratia abundance and downregulation of innate cytokines allowed re-establishment of systemic T cell homeostasis promoting restoration of Th1 and Th2 gene expression signatures. Analyses of three other geographically distinct cohorts of treated HIV infection established a more generalized principle that changes in diversity and composition of translocated microbial species influence systemic inflammation and consequently CD4 T cell recovery.

Additional Organisation(s)

Institute of Clinical and Molecular Virology

Involved external institutions

Case Western Reserve University US United States (USA) (US) Joint Clinical Research Centre UG Uganda (UG) National Institute of Allergy and Infectious Diseases US United States (USA) (US) University of Minnesota (UMN) US United States (USA) (US) Centre hospitalier de l'Université de Montréal (CHUM) CA Canada (CA) University of Miami US United States (USA) (US)

How to cite

APA:

Nganou-Makamdop, K., Talla, A., Sharma, A.A., Darko, S., Ransier, A., Laboune, F.,... Douek, D.C. (2021). Translocated microbiome composition determines immunological outcome in treated HIV infection. Cell, 184(15), 3899-3914.e16. https://doi.org/10.1016/j.cell.2021.05.023

MLA:

Nganou-Makamdop, Krystelle, et al. "Translocated microbiome composition determines immunological outcome in treated HIV infection." Cell 184.15 (2021): 3899-3914.e16.

BibTeX: Download