PMID- 31456797 OWN - NLM STAT- MEDLINE DCOM- 20200930 LR - 20200930 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Changes in the NK Cell Repertoire Related to Initiation of TB Treatment and Onset of Immune Reconstitution Inflammatory Syndrome in TB/HIV Co-infected Patients in Rio de Janeiro, Brazil-ANRS 12274. PG - 1800 LID - 10.3389/fimmu.2019.01800 [doi] LID - 1800 AB - Tuberculosis (TB) is the most common comorbidity and the leading cause of death among HIV-infected individuals. Although the combined antiretroviral therapy (cART) during TB treatment improves the survival of TB/HIV patients, the occurrence of immune reconstitution inflammatory syndrome (IRIS) in some patients poses clinical and scientific challenges. This work aimed to evaluate blood innate lymphocytes during therapeutic intervention for both diseases and their implications for the onset of IRIS. Natural killer (NK) cells, invariant NKT cells (iNKT), gammadelta T cell subsets, and in vitro NK functional activity were characterized by multiparametric flow cytometry in the following groups: 33 TB/HIV patients (four with paradoxical IRIS), 27 TB and 25 HIV mono-infected subjects (prior to initiation of TB treatment and/or cART and during clinical follow-up to 24 weeks), and 25 healthy controls (HC). Concerning the NK cell repertoire, several activation and inhibitory receptors were skewed in the TB/HIV patients compared to those in the other groups, especially the HCs. Significantly higher expression of CD158a (p = 0.025), NKp80 (p = 0.033), and NKG2C (p = 0.0076) receptors was detected in the TB/HIV IRIS patients than in the non-IRIS patients. Although more NK degranulation was observed in the TB/HIV patients than in the other groups, the therapeutic intervention did not alter the frequency during follow-up (weeks 2-24). A higher frequency of the gammadelta T cell population was observed in the TB/HIV patients with inversion of the Vdelta2(+)/Vdelta2(-) ratio, especially for those presenting pulmonary TB, suggesting an expansion of particular gammadelta T subsets during TB/HIV co-infection. In conclusion, HIV infection impacts the frequency of circulating NK cells and gammadelta T cell subsets in TB/HIV patients. Important modifications of the NK cell repertoire were observed after anti-TB treatment (week 2) but not during the cART/TB follow-up (weeks 6-24). An increase of CD161(+) NK cells was related to an unfavorable outcome. Despite the low number of cases, a more preserved NK cell profile was detected in IRIS patients previous to treatment, suggesting a role for these cells in IRIS onset. Longitudinal evaluation of the NK repertoire showed the impact of TB treatment and implicated these cells in TB pathogenesis in TB/HIV co-infected patients. FAU - Giacoia-Gripp, Carmem Beatriz Wagner AU - Giacoia-Gripp CBW AD - Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Cazote, Andressa da Silva AU - Cazote ADS AD - Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, Brazil. FAU - da Silva, Tatiana Pereira AU - da Silva TP AD - Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Sant'Anna, Flavia Marinho AU - Sant'Anna FM AD - Clinical Research Laboratory on Mycobacteria, National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Schmaltz, Carolina Arana Stanis AU - Schmaltz CAS AD - Clinical Research Laboratory on Mycobacteria, National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Brum, Tania de Souza AU - Brum TS AD - HIV Clinical Research Center, Nova Iguacu General Hospital (HGNI), Rio de Janeiro, Brazil. FAU - de Matos, Juliana Arruda AU - de Matos JA AD - Clinical Research Laboratory on Health Surveillance and Immunization, National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Silva, Julio AU - Silva J AD - Platform for Clinical Research, National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Benjamin, Aline AU - Benjamin A AD - Clinical Research Laboratory on Mycobacteria, National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Pilotto, Jose Henrique AU - Pilotto JH AD - Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, Brazil. AD - HIV Clinical Research Center, Nova Iguacu General Hospital (HGNI), Rio de Janeiro, Brazil. FAU - Rolla, Valeria Cavalcanti AU - Rolla VC AD - Clinical Research Laboratory on Mycobacteria, National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Morgado, Mariza Goncalves AU - Morgado MG AD - Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute (FIOCRUZ), Rio de Janeiro, Brazil. FAU - Scott-Algara, Daniel AU - Scott-Algara D AD - Unit of Lymphocyte Cell Biology, Pasteur Institute, Paris, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190813 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Anti-HIV Agents) RN - 0 (Antitubercular Agents) SB - IM MH - Adult MH - Anti-HIV Agents/therapeutic use MH - Antitubercular Agents/therapeutic use MH - Brazil MH - Coinfection/immunology MH - Female MH - Flow Cytometry MH - Follow-Up Studies MH - HIV Infections/complications/drug therapy/*immunology MH - Humans MH - Immune Reconstitution Inflammatory Syndrome/etiology/*immunology MH - Immunity, Innate MH - Killer Cells, Natural/*immunology MH - Male MH - Middle Aged MH - T-Lymphocyte Subsets/immunology MH - Treatment Outcome MH - Tuberculosis, Pulmonary/complications/drug therapy/*immunology PMC - PMC6700218 OTO - NOTNLM OT - IRIS OT - NK cell repertoire OT - TB/HIV Co-infection OT - clinical outcomes OT - innate immune cells EDAT- 2019/08/29 06:00 MHDA- 2020/10/02 06:00 PMCR- 2019/01/01 CRDT- 2019/08/29 06:00 PHST- 2019/05/01 00:00 [received] PHST- 2019/07/17 00:00 [accepted] PHST- 2019/08/29 06:00 [entrez] PHST- 2019/08/29 06:00 [pubmed] PHST- 2020/10/02 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.01800 [doi] PST - epublish SO - Front Immunol. 2019 Aug 13;10:1800. doi: 10.3389/fimmu.2019.01800. eCollection 2019.