Translocated microbiome composition determines immunological outcome in treated HIV infection

Krystelle Nganou-Makamdop; Aarthi Talla; Ashish Arunkumar Sharma; Sam Darko; Amy Ransier; Farida Laboune; Jeffrey G. Chipman; Gregory J. Beilman; Torfi Hoskuldsson; Slim Fourati; Thomas E. Schmidt; Sahaana Arumugam; Noemia S. Lima; Damee Moon; Samuel Callisto; Jordan Schoephoerster; Jeffery Tomalka; Peter Mugyenyi; Francis Ssali; Proscovia Muloma; Patrick Ssengendo; Ana R. Leda; Ryan K. Cheu; Jacob K. Flynn; Antigoni Morou; Elsa Brunet-Ratnasingham; Benigno Rodriguez; Michael M. Lederman; Daniel E. Kaufmann; Nichole R. Klatt; Cissy Kityo; Jason M. Brenchley; Timothy W. Schacker; Rafick P. Sekaly; Daniel C. Douek

doi:10.1016/j.cell.2021.05.023

Translocated microbiome composition determines immunological outcome in treated HIV infection

Krystelle Nganou-Makamdop, Aarthi Talla, Ashish Arunkumar Sharma, Sam Darko, Amy Ransier, Farida Laboune, Jeffrey G. Chipman, Gregory J. Beilman, Torfi Hoskuldsson, Slim Fourati, Thomas E. Schmidt, Sahaana Arumugam, Noemia S. Lima, Damee Moon, Samuel Callisto, Jordan Schoephoerster, Jeffery Tomalka, Peter Mugyenyi, Francis Ssali, Proscovia MulomaPatrick Ssengendo, Ana R. Leda, Ryan K. Cheu, Jacob K. Flynn, Antigoni Morou, Elsa Brunet-Ratnasingham, Benigno Rodriguez, Michael M. Lederman, Daniel E. Kaufmann, Nichole R. Klatt, Cissy Kityo, Jason M. Brenchley, Timothy W. Schacker, Rafick P. Sekaly, Daniel C. Douek

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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.

Original language	English (US)
Pages (from-to)	3899-3914.e16
Journal	Cell
Volume	184
Issue number	15
DOIs	https://doi.org/10.1016/j.cell.2021.05.023
State	Published - Jul 22 2021

Bibliographical note

Publisher Copyright:
© 2021

Keywords

HIV
antiretroviral therapy
inflammation
microbiome
systems biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Nganou-Makamdop, K., Talla, A., Sharma, A. A., Darko, S., Ransier, A., Laboune, F., Chipman, J. G., Beilman, G. J., Hoskuldsson, T., Fourati, S., Schmidt, T. E., Arumugam, S., Lima, N. S., Moon, D., Callisto, S., Schoephoerster, J., Tomalka, J., Mugyenyi, P., Ssali, 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

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, 'Translocated microbiome composition determines immunological outcome in treated HIV infection', Cell, vol. 184, no. 15, pp. 3899-3914.e16. https://doi.org/10.1016/j.cell.2021.05.023

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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.",

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AU - Ransier, Amy

AU - Laboune, Farida

AU - Chipman, Jeffrey G.

AU - Beilman, Gregory J.

AU - Hoskuldsson, Torfi

AU - Fourati, Slim

AU - Schmidt, Thomas E.

AU - Arumugam, Sahaana

AU - Lima, Noemia S.

AU - Moon, Damee

AU - Callisto, Samuel

AU - Schoephoerster, Jordan

AU - Tomalka, Jeffery

AU - Mugyenyi, Peter

AU - Ssali, Francis

AU - Muloma, Proscovia

AU - Ssengendo, Patrick

AU - Leda, Ana R.

AU - Cheu, Ryan K.

AU - Flynn, Jacob K.

AU - Morou, Antigoni

AU - Brunet-Ratnasingham, Elsa

AU - Rodriguez, Benigno

AU - Lederman, Michael M.

AU - Kaufmann, Daniel E.

AU - Klatt, Nichole R.

AU - Kityo, Cissy

AU - Brenchley, Jason M.

AU - Schacker, Timothy W.

AU - Sekaly, Rafick P.

AU - Douek, Daniel C.

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JF - Cell

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ER -

Translocated microbiome composition determines immunological outcome in treated HIV infection

Abstract

Bibliographical note

Keywords

UN SDGs

Access

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