Inflammasome genetics contributes to the development and control of active pulmonary tuberculosis.
Tuberculosis (TB) continues to be a major public health problem. An estimated one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb) but remains asymptomatic (latent TB) and only 5% to 10% of these latent individuals will develop active pulmonary TB. Factors affecting the balance between latent and active TB are mostly unknown, even if host genome has been shown to contribute to the outcome of Mtb response. Acute inflammation and Th1 response are important in the early clearance of the bacteria as it was emphasized by the association between immune genes (i.e.: HLA, IFNG, TNF, NRPAM1, IL10) variants and the development of active pulmonary TB. Recently, the role of the inflammasome in experimental TB has been demonstrated, however, to our knowledge, no data still exist about the contribution of inflammasome genetics to Mtb susceptibility and/or to the development of active TB. For this reason, selected polymorphisms in inflammasome genes were analysed in a case/control cohort of individuals with active pulmonary TB from an endemic area of Brazil Amazon. Our data evidence the novel association between polymorphisms in NLRP3-inflammasome encoding genes and active pulmonary TB, and replicated the association between P2X7 and TB observed in other populations. These results emphasize the role of NLRP3-inflammasome also in human TB, and contribute to our knowledge about pathways involved in the development of active TB, even if deeper investigation are needed to fully elucidate the role of the complex in Mtb infection.
Laboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil; Laboratório Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM, Brazil. Electronic address: dhemersonsouzalima@gmail.com.
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Souza de Lima
Laboratório de Micobacteriologia, Institut oNacional de Pesquisas da Amazônia, Manaus, AM, Brazil.
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Ogusku
Laboratório Imunologia Molecular, Departamento de Parasitologia, Universidade Federal do Amazonas, Manaus, AM, Brazil.
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Sadahiro
Laboratório de Imunogenética, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
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Pontillo
D000328:Adult; D001938:Brazil; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002401:Cathepsin B / Q000235:genetics* / Q000276:immunology; D060467:Disease Resistance / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D058847:Inflammasomes / Q000235:genetics* / Q000276:immunology; D055985:Latent Tuberculosis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000254:growth & development; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics* / Q000276:immunology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D058486:Receptors, Purinergic P2X7 / Q000235:genetics* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology
D053468:CARD Signaling Adaptor Proteins; C455623:CARD8 protein, human; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D009363:Neoplasm Proteins; D058486:Receptors, Purinergic P2X7; C533912:CTSB protein, human; D002401:Cathepsin B
CARD8; CTSB; Inflammasome; NLRP3; P2X7; PULMONARY TB; polymorphisms