High abundance of genus Prevotella is associated with dysregulation of IFN-I and T cell response in HIV-1-infected patients.


Journal

AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219

Informations de publication

Date de publication:
01 08 2020
Historique:
entrez: 18 7 2020
pubmed: 18 7 2020
medline: 20 2 2021
Statut: ppublish

Résumé

HIV-1-associated dysbiosis is most commonly characterized by overall decreased diversity, with abundance of the genus Prevotella, recently related to inflammatory responses. A pilot study including 10 antiretroviral therapy-treated HIV-1-infected men and 50 uninfected controls was performed to identify the main gut dysbiosis determinants (e.g. Prevotella enrichment), that may affect mucosal antiviral defenses and T cell immunity in HIV-1-infected individuals. 16rRNA gene sequencing was applied to the HIV-1-infected individuals' fecal microbiota and compared with controls. Measurements of CD4 and CD8 T cell activation [CD38, human leukocyte antigen (HLA)-DR, CD38 HLA-DR] and frequencies of Th17, obtained from lamina propria lymphocytes isolated from five different intestinal sites, were performed by flow cytometry. IFNβ, IFNAR1 and MxA gene expression level was evaluated by real-time PCR in lamina propria lymphocytes. Nonparametric t tests were used for statistical analysis. HIV-1-infected men had a significant fecal microbial communities' imbalance, including different levels of genera Faecalibacterium, Prevotella, Alistipes and Bacteroides, compared with controls. Notably, Prevotella abundance positively correlated with frequencies of CD4 T cells expressing CD38 or HLA-DR and coexpressing CD38 and HLA-DR (P < 0.05 for all these measures). The same trend was observed for the activated CD8 T cells. Moreover, Prevotella levels were inversely correlated with IFN-I genes (P < 0.05 for IFNβ, IFNAR1 and MxA genes) and the frequencies of Th17 cells (P < 0.05). By contrast, no statistically significant correlations were observed for the remaining bacterial genera. Our findings suggest that Prevotella enrichment might affect gut mucosal IFN-I pathways and T cell response in HIV-1-infected patients, thus contributing to immune dysfunction.

Identifiants

pubmed: 32675560
doi: 10.1097/QAD.0000000000002574
pii: 00002030-202008010-00005
doi:

Substances chimiques

HLA-DR Antigens 0
IFNAR1 protein, human 0
MX1 protein, human 0
Myxovirus Resistance Proteins 0
Receptor, Interferon alpha-beta 156986-95-7
Interferon-beta 77238-31-4
ADP-ribosyl Cyclase 1 EC 3.2.2.6

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1467-1473

Références

Dillon SM, Frank DN, Wilson CC. The gut microbiome and HIV-1 pathogenesis: a two-way street. AIDS 2016; 30:2737–2751.
Nowak P, Troseid M, Avershina E, Barqasho B, Neogi U, Holm K, et al. Gut microbiota diversity predicts immune status in HIV-1 infection. AIDS 2015; 29:2409–2418.
Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, et al. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med 2013; 5:193ra191.
Mutlu EA, Keshavarzian A, Losurdo J, Swanson G, Siewe B, Forsyth C, et al. A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects. PLoS Pathog 2014; 10:e1003829.
Lozupone CA, Li M, Campbell TB, Flores SC, Linderman D, Gebert MJ, et al. Alterations in the gut microbiota associated with HIV-1 infection. Cell Host Microbe 2013; 14:329–339.
Dillon SM, Lee EJ, Kotter CV, Austin GL, Gianella S, Siewe B, et al. Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection. Mucosal Immunol 2016; 9:24–37.
Kumar PS, Griffen AL, Barton JA, Paster BJ, Moeschberger ML, Leys EJ. New bacterial species associated with chronic periodontitis. J Dent Res 2003; 82:338–344.
Lucke K, Miehlke S, Jacobs E, Schuppler M. Prevalence of Bacteroides and Prevotella spp. in ulcerative colitis. J Med Microbiol 2006; 55 (Pt 5):617–624.
Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2013; 2:e01202.
Kehrmann J, Menzel J, Saeedghalati M, Obeid R, Schulze C, Holzendorf V, et al. Gut microbiota in human immunodeficiency virus-infected individuals linked to coronary heart disease. J Infect Dis 2019; 219:497–508.
Ciccone EJ, Read SW, Mannon PJ, Yao MD, Hodge JN, Dewar R, et al. Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels. Mucosal Immunol 2010; 3:172–181.
Dillon SM, Manuzak JA, Leone AK, Lee EJ, Rogers LM, McCarter MD, et al. HIV-1 infection of human intestinal lamina propria CD4+ T cells in vitro is enhanced by exposure to commensal Escherichia coli. J Immunol 2012; 189:885–896.
d’Ettorre G, Rossi G, Scagnolari C, Andreotti M, Giustini N, Serafino S, et al. Probiotic supplementation promotes a reduction in T-cell activation, an increase in Th17 frequencies, and a recovery of intestinal epithelium integrity and mitochondrial morphology in ART-treated HIV-1-positive patients. Immun Inflamm Dis 2017; 5:244–260.
Iebba V, Guerrieri F, Di Gregorio V, Levrero M, Gagliardi A, Santangelo F, et al. Combining amplicon sequencing and metabolomics in cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy. Sci Rep 2018; 8:8210.
Statzu M, Santinelli L, Viscido A, Pinacchio C, Ceccarelli G, Rotondo C, et al. Increased SAMHD1 transcript expression correlates with interferon-related genes in HIV-1-infected patients. Med Microbiol Immunol 2019; 208:679–691.
d’Ettorre G, Borrazzo C, Pinacchio C, Santinelli L, Cavallari EN, Statzu M, et al. Increased IL-17 and/or IFN-γ producing T-cell subsets in gut mucosa of long-term-treated HIV-1-infected women. AIDS 2019; 33:627–636.
Crakes KR, Jiang G. Gut microbiome alterations during HIV/SIV infection: implications for HIV cure. Front Microbiol 2019; 10:1104.
Liu J, Williams B, Frank D, Dillon SM, Wilson CC, Landay AL. Inside out: HIV, the gut microbiome, and the mucosal immune system. J Immunol 2017; 198:605–614.
Scagnolari C, Antonelli G. Type I interferon and HIV: subtle balance between antiviral activity, immunopathogenesis and the microbiome. Cytokine Growth Factor Rev 2018; 40:19–31.
Neff CP, Krueger O, Xiong K, Arif S, Nusbacher N, Schneider JM, et al. Fecal microbiota composition drives immune activation in HIV-infected individuals. EBioMedicine 2018; 30:192–202.
Dillon SM, Lee EJ, Kotter CV, Austin GL, Dong Z, Hecht DK, et al. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol 2014; 7:983–994.
Paquin-Proulx D, Ching C, Vujkovic-Cvijin I, Fadrosh D, Loh L, Huang Y, et al. Bacteroides are associated with GALT iNKT cell function and reduction of microbial translocation in HIV-1 infection. Mucosal Immunol 2017; 10:69–78.
Kaur US, Shet A, Rajnala N, Gopalan BP, Moar PDH, Singh BP, et al. High abundance of genus prevotella in the gut of perinatally HIV-infected children is associated with IP-10 levels despite therapy. Sci Rep 2018; 8:17679.
McHardy IH, Li X, Tong M, Ruegger P, Jacobs J, Borneman J, et al. HIV Infection is associated with compositional and functional shifts in the rectal mucosal microbiota. Microbiome 2013; 1:26.
Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature 2011; 473:174–180.
De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A 2010; 107:14691–14696.
Ickler J, Francois S, Widera M, Santiago ML, Dittmer U, Sutter K. HIV infection does not alter interferon α/β receptor 2 expression on mucosal immune cells. PLoS One 2020; 15:e0218905.
Dillon M, Guo K, Austin GL, Gianella S, Engen PA, Mutlu EA, et al. A compartmentalized type I interferon response in the gut during chronic HIV-1 infection is associated with immunopathogenesis. AIDS 2018; 32:1599–1611.
Pinacchio C, Scheri GC, Statzu M, Santinelli L, Ceccarelli G, Innocenti GP, et al. Type I/II interferon in HIV-1-infected patients: expression in gut mucosa and in peripheral blood mononuclear cells and its modification upon probiotic supplementation. J Immunol Res 2018; 2018:1738676.
Glavan TW, Gaulke CA, Santos Rocha C, Sankaran-Walters S, Hirao LA, Raffatellu M, et al. Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection. Mucosal Immunol 2016; 9:677–688.
Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 2012; 37:158–170.
Vázquez-Castellanos JF, Serrano-Villar S, Latorre A, Artacho A, Ferrús ML, Madrid N, et al. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals. Mucosal Immunol 2015; 8:760–772.
Elhed A, Unutmaz D. Th17 cells and HIV infection. Curr Opin HIV AIDS 2010; 5:146–150.
Tincati C, Douek DC, Marchetti G. Gut barrier structure, mucosal immunity and intestinal microbiota in the pathogenesis and treatment of HIV infection. AIDS Res Ther 2016; 13:19.
Ling Z, Jin C, Xie T, Cheng Y, Li L, Wu N. Alterations in the fecal microbiota of patients with HIV-1 infection: an observational study in a Chinese population. Sci Rep 2016; 6:30673.
Dubourg G, Lagier JC, Hüe S, Surenaud M, Bachar D, Robert C, et al. Gut microbiota associated with HIV infection is significantly enriched in bacteria tolerant to oxygen. BMJ Open Gastroenterol 2016; 3:e000080.
Zhou L, Zhang M, Wang Y, Dorfman RG, Liu H, Yu T, et al. Faecalibacterium prausnitzii produces butyrate to maintain Th17/Treg balance and to ameliorate colorectal colitis by inhibiting histone deacetylase 1. Inflamm Bowel Dis 2018; 24:1926–1940.
Williams B, Landay A, Presti RM. Microbiome alterations in HIV infection a review. Cell Microbiol 2016; 18:645–651.
Reikvam DH, Meyer-Myklestad MH, Trøseid M, Stiksrud B. Probiotics to manage inflammation in HIV infection. Curr Opin Infect Dis 2020; 33:34–43.
Ceccarelli G, Statzu M, Santinelli L, Pinacchio C, Bitossi C, Cavallari EN, et al. Challenges in the management of HIV infection: update on the role of probiotic supplementation as a possible complementary therapeutic strategy for cART treated people living with HIV/AIDS. Expert Opin Biol Ther 2019; 19:949–965.

Auteurs

Claudia Pinacchio (C)

Department of Public Health and Infectious Diseases.

Carolina Scagnolari (C)

Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome.

Valerio Iebba (V)

Institute for Maternal and Child Health-IRCCS 'Burlo Garofolo'.
Department of Medical Sciences, University of Trieste, Trieste.

Letizia Santinelli (L)

Department of Public Health and Infectious Diseases.

Giuseppe P Innocenti (GP)

Department of Public Health and Infectious Diseases.

Federica Frasca (F)

Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome.

Camilla Bitossi (C)

Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome.

Mirko Scordio (M)

Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome.

Giuseppe Oliveto (G)

Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome.

Giancarlo Ceccarelli (G)

Department of Public Health and Infectious Diseases.

Guido Antonelli (G)

Laboratory of Virology, Department of Molecular Medicine, Istituto Pasteur Italia, Sapienza University, Rome.
Microbiology and Virology Unit, Sapienza University, Hospital Policlinico Umberto I, Rome, Italy.

Claudio Maria Mastroianni (CM)

Department of Public Health and Infectious Diseases.

Gabriella d'Ettorre (G)

Department of Public Health and Infectious Diseases.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH