Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes.

Autor:	de Sá NBR; 1Laboratory of AIDS & Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., de Souza NCS; 1Laboratory of AIDS & Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Neira-Goulart M; 1Laboratory of AIDS & Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Ribeiro-Alves M; Laboratory of Clinical Research on STD/AIDS, National Institute of Infectious Diseases Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil., Da Silva TP; 1Laboratory of AIDS & Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Pilotto JH; 1Laboratory of AIDS & Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.; Nova Iguaçu General Hospital, Nova Iguaçu, Rio de Janeiro, Brazil., Rolla VC; Clinical Research Laboratory on Mycobacteria, National Institute of Infectious Diseases Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil., Giacoia-Gripp CBW; 1Laboratory of AIDS & Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., de Oliveira Pinto LM; Laboratory of Viral Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Scott-Algara D; Unité de Biologie Cellulaire des Lymphocytes, Institut Pasteur, Paris, France., Morgado MG; 1Laboratory of AIDS & Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil., Teixeira SLM; 1Laboratory of AIDS & Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2022 Sep 20; Vol. 12, pp. 962059. Date of Electronic Publication: 2022 Sep 20 (Print Publication: 2022).
DOI:	10.3389/fcimb.2022.962059
Abstrakt:	Background: Tuberculosis (TB) and AIDS are the leading causes of infectious diseases death worldwide. Here, we investigated the relationship between from single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1β inflammasome genes, as well as the profiles of secreted proinflammatory cytokines (e.g., IL-1β, IL-18, IL-33, and IL-6) with the TB clinical profiles, TB-HIV coinfection, and IRIS onset. Methods: The individuals were divided into four groups: TB-HIV group (n=88; 11 of them with IRIS), HIV-1 group (n=20), TB group (n=24) and healthy volunteers (HC) group (n=10), and were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. Real-time PCR was used to determine the genotypes of the Single Nucleotide Polymorphism (SNPs), and ELISA was used to measure the plasma cytokine levels. Unconditional logistic regression models were used to perform risk estimations. Results: A higher risk for extrapulmonary TB was associated with the TT genotype (aOR=6.76; P=0.026) in the NLRP3 rs4612666 Single Nucleotide Polymorphism (SNP) and the C-C-T-G-C haplotype (aOR=4.99; P= 0.017) in the NLRP3 variants. This same Single Nucleotide Polymorphism (SNP) was associated with lower risk against extrapulmonary TB when the carrier allele C (aOR=0.15; P=0.021) was present. Among those with HIV-1 infections, a higher risk for TB onset was associated with the GA genotype (aOR=5.5; P=0.044) in the IL1-β rs1143634 Single Nucleotide Polymorphism (SNP). In contrast, lower risk against TB onset was associated with the A-G haplotype (aOR=0.17; P= 0.026) in the CARD8 variants. Higher IL-6 and IL-33 levels were observed in individuals with TB. A higher risk for IRIS onset was associated with CD8 counts ≤ 500 cells/mm 3 (aOR=12.32; P=0.010), the presence of extrapulmonary TB (aOR=6.6; P=0.038), and the CT genotype (aOR=61.06; P=0.026) or carrier allele T (aOR=61.06; P=0.026) in the AIM2 rs2276405 Single Nucleotide Polymorphism (SNP), whereas lower risk against IRIS onset was associated with the AT genotype (aOR=0.02; P=0.033) or carrier allele T (aOR=0.02; P=0.029) in the CARD8 rs2043211 Single Nucleotide Polymorphism (SNP) and the T-G haplotype (aOR=0.07; P= 0.033) in the CARD8 variants. No other significant associations were observed. Conclusions: Our results depict the involvement of genetic polymorphisms of crucial innate immunity genes and proinflammatory cytokines in the clinical outcomes related to TB-HIV coinfection. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 de Sá, de Souza, Neira-Goulart, Ribeiro-Alves, Da Silva, Pilotto, Rolla, Giacoia-Gripp, de Oliveira Pinto, Scott-Algara, Morgado and Teixeira.)
Databáze:	MEDLINE
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