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Your search keyword '"Vinicius M. Fava"' showing total 2 results
Start Over Author "Vinicius M. Fava" Journal frontiers in immunology
2 results on '"Vinicius M. Fava"'

1. Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis

Author

Jean-Yves Dubé, Vinicius M. Fava, Erwin Schurr, and Marcel A. Behr

Subjects
mycobacterium tuberculosis, tuberculosis, pattern recognition receptor (PRR), genetic association studies (GAS), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), Immunologic diseases. Allergy, RC581-607
Abstract

Human genetic control is thought to affect a considerable part of the outcome of infection with Mycobacterium tuberculosis (Mtb). Most of us deal with the pathogen by containment (associated with clinical “latency”) or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility to Mtb infection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease. Genes encoding pattern recognition receptors (PRRs) enable a consistent, molecularly direct interaction between humans and Mtb which suggests the potential for co-evolution. In this review, we explore the roles ascribed to PRRs during Mtb infection and ask whether such a longstanding and intimate interface between our immune system and this pathogen plays a critical role in determining the outcome of Mtb infection. The scientific evidence to date suggests that PRR variation is clearly implicated in altered immunity to Mtb but has a more subtle role in limiting the pathogen and pathogenesis. In contrast to ‘effectors’ like IFN-γ, IL-12, Nitric Oxide and TNF that are critical for Mtb control, ‘sensors’ like PRRs are less critical for the outcome of Mtb infection. This is potentially due to redundancy of the numerous PRRs in the innate arsenal, such that Mtb rarely goes unnoticed. Genetic association studies investigating PRRs during Mtb infection should therefore be designed to investigate endophenotypes of infection – such as immunological or clinical variation – rather than just TB disease, if we hope to understand the molecular interface between innate immunity and Mtb.

Published
2021
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2. Age-Dependent Association of TNFSF15/TNFSF8 Variants and Leprosy Type 1 Reaction

Author

Milton Ozório Moraes, Alexandre Alcaïs, Vinicius M. Fava, Carolinne Sales-Marques, and Erwin Schurr

Subjects
0301 basic medicine, Crohn’s disease, age at disease diagnosis, excessive inflammatory response, Vietnamese, Population, Immunology, Biology, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, TNFSF8, education, Gene, Pathological, Genetic association, Original Research, Genetics, education.field_of_study, TNFSF15, type 1 reaction, Odds ratio, medicine.disease, language.human_language, Confidence interval, 3. Good health, 030104 developmental biology, association studies, 030220 oncology & carcinogenesis, language, Leprosy, leprosy
Abstract

A current major challenge in leprosy control is the prevention of permanent disabilities. Host pathological inflammatory responses termed type 1 reaction (T1R) are a leading cause of nerve damage for leprosy patients. The environmental or inherited factors that predispose leprosy cases to undergo T1R are not known. However, studies have shown an important contribution of host genetics for susceptibility to T1R. We have previously identified variants encompassing the TNFSF15/TNFSF8 genes as T1R risk factors in a Vietnamese sample and replicated this association in a Brazilian sample. However, we failed to validate in Brazilian patients the strong association of TNFSF15/TNFSF8 markers rs6478108 and rs7863183 with T1R that we had observed in Vietnamese patients. Here, we investigated if the lack of validation of these variants was due to age-dependent effects on association using four independent population samples, two from Brazil and two from Vietnam. In the combined analysis across the four samples, we observed a strong association of the TNFSF15/TNFSF8 variants rs6478108, rs7863183, and rs3181348 with T1R (pcombined = 1.5E-05, pcombined = 1.8E-05, and pcombined = 6.5E-06, respectively). However, the association of rs6478108 with T1R was more pronounced in leprosy cases under 30 years of age compared to the global sample [odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.54-2.46, pcombined = 2.5E-08 versus OR = 1.46, 95% CI = 1.23-1.73, pcombined = 1.5E-05]. A multivariable analysis indicated that the association of rs6478108 with T1R was independent of either rs7863183 or rs3181348. These three variants are known regulators of the TNFSF8 gene transcription level in multiple tissues. The age dependency of association of rs6478108 and T1R suggests that the genetic control of gene expression varies across the human life span.

Published
2017

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