| Full text | |
| Author(s): Show less - |
De Lima, Dhemerson Souza
[1]
;
Bomfim, Caio C. B.
[2]
;
Leal, Vinicius N. C.
[1]
;
Reis, Edione C.
[1]
;
Soares, Jaine L. S.
[1]
;
Fernandes, Fernanda P.
[1]
;
Amaral, Eduardo P.
[2]
;
Loures, V, Flavio
;
Ogusku, Mauricio M.
[3]
;
D'Imperio Lima, Maria R.
[2]
;
Sadahiro, Aya
[4]
;
Pontillo, Alessandra
[1]
Total Authors: 12
|
| Affiliation: | [1] Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, Lab Imunogenet, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Doencas Infecciosas, Sao Paulo - Brazil
[3] Inst Nacl de Pesquisas da Amazonia, Lab Micobacteriol, Manaus, Amazonas - Brazil
[4] Univ Fed Amazonas, Dept Parasitol, Manaus, Amazonas - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | FRONTIERS IN IMMUNOLOGY; v. 11, OCT 21 2020. |
| Web of Science Citations: | 0 |
| Abstract | |
The interplay between M. tuberculosis (Mtb) and humans is multifactorial. The susceptibility/resistance profile and the establishment of clinical tuberculosis (TB) still remains elusive. The gain-of-function variant rs10754558 in the NLRP3 gene (found in 30% of the world population) confers protection against the development of TB, indicating a prominent role played by NLRP3 inflammasome against Mtb. Through genotype-guided assays and various Mtb strains (BCG, H37Rv, Beijing-1471, MP287/03), we demonstrate that Mtb strains activate inflammasome according to the NLRP3/IL-1ss or NLRC4/IL18 preferential axis. NLRP3 and NLRC4 genetic variants contribute to the presentation of TB. For the first time, we have shown that loss-of-function variants in NLRC4 significantly contribute to the development of extra-pulmonary TB. The analysis of inflammasome activation in a cohort of TB patients and their ``household contacts{''} (CNT) revealed that plasma IL-1ss/IFN-alpha ratio lets us distinguish patients from Mtb-exposed-but-healthy individuals from an endemic region. Moreover, NLRP3 inflammasome seemed ``exhausted{''} in TB patients compared to CNT, indicating a more efficient activation of inflammasome in resistant individuals. These findings suggest that inflammasome genetics as well as virulence-dependent level of inflammasome activation contribute to the onset of a susceptible/resistant profile among Mtb-exposed individuals. (AU) | |
| FAPESP's process: | 15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis |
| Grantee: | Maria Regina D'Império Lima |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 15/23395-6 - Immunogenetics of the inflammasome and translational study "from bed to bench and back": analysis of variations in inflammasome genes in monogenic and multifactorial autoinflammatory diseases for differential diagnosis and therapeutic applications |
| Grantee: | Alessandra Pontillo |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 15/50650-7 - Characterization of novel molecular players in the control of obesity and obesity-induced inflammation |
| Grantee: | Alessandra Pontillo |
| Support Opportunities: | Regular Research Grants |