The host-pathogen-environment triad: Lessons learned through the study of the multidrug-resistant Mycobacterium tuberculosis M strain

Yokobori, Noemí; López, Beatriz; Ritacco, Viviana

doi:10.1016/j.tube.2022.102200

Cited by 4 publications

(3 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They showed that as in the rest of South America, genotypes of the Lineage 4 Euro-American (one of the seven globally described M. tuberculosis strains) predominate in our country and in contrast with the neighboring country Brazil, the RD rio type (associated with high rate of transmission and drug resistance) does not play a major role in the TB epidemic ( Monteserin et al., 2018 ). Moreover, the multidrug resistant M strain which belongs to the Lineage 4 Euro-American is highly prevalent in Argentina and has been shown to induce poor immune responses ( Yokobori et al., 2022 ). However, the M. tuberculosis population structure in Argentina is still not fully comprehend.…”

Section: Discussionmentioning

confidence: 99%

Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility

Álvarez

Pino²,

Barbero³

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

IntroductionTuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription.MethodsWe evaluated both genetic and epigenetic changes involved in IFN-γ production and TB susceptibility in Argentine population. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed for the IFN-γ +874 A/T polymorphism (rs2430561) genotyping in 199 healthy donors (HD) and 173 tuberculosis (TB) patients. IFN-γ levels from M. tuberculosis-stimulated PBMCs were measured by ELISA. The methylation status at the -53 CpG site of the IFNG promoter in individuals with latent infection (LTBI), TB and HD was determine by pyrosequencing.ResultsUsing a case-control study, we found that A allele and, consequently, AA genotype were overrepresented in patients with active disease. Moreover, HD carrying T allele (AT or TT genotype) evidenced an augmented IFN-γ secretion compared to TB patients. Codominance was the genetic model that best fits our results according to the Akaike information criterion (AIC). In addition, increased methylation levels at the -53 CpG site in the IFN-γ promoter were observed in whole blood of patients with active TB compared to LTBI individuals.DiscussionIFN-γ is regulated by genetic variants and epigenetic modifications during TB. Besides, AA genotype of the rs2430561 single nucleotide polymorphism could be considered as a potential TB susceptibility genetic biomarker in Argentina and the methylation of the -53 CpG site could result in a useful predictor of TB reactivation.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility

Álvarez

Pino²,

Barbero³

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Environment, pathogen, immunity, which are the triad affects each other and gives healthiness from nowadays public health perspective [10]. Overall, it is the idea of relevant adaptation of human body to natural environment(tian ren xiangying 天人相應) in TCM.…”

Section: Clinical Considerations Based On Macrocosmic Influencesmentioning

confidence: 99%

“…Modern epidemiology has a triangular relationship referring to host-pathogen-environment triad [10]. There is a concise explanation of the mechanism how climate change affecting our health plays an important role to our environment which may give the opportunity of the influenza virus to affecting our immunological system and causing vast epidemic contagious diseases.…”

Section: Contribution Of Ancient Tcmmentioning

confidence: 99%

Untitled

2023

ACIM

View full text Add to dashboard Cite

It is clear that we must obtain knowledge of the primary causes, because it is when we think that we understand its primary cause that we claim to know each particular thing." In the topic of being a scientist, Aristotle expounded the differences between a craftsman or a wiseman. Craftsman is the one who has had experiences but not the wherefore. He further explained that master craftsmen are superior in

show abstract

Variants of human DECTIN-1 rs16910526 are linked to differential reactive oxygen species production and susceptibility to tuberculosis

Cufré,

Pastorini,

Martín

et al. 2024

J Biomed Sci

View full text Add to dashboard Cite

Background Dectin-1 is a transmembrane receptor that plays a pivotal role in recognising fungi and Mycobacterium tuberculosis (Mtb). A specific variant, DECTIN-1 rs16910526, results in a truncated receptor that disrupts membrane expression and ligand binding and is clinically associated with recurrent cutaneous mycoses. Previous research has clarified the role of Dectin-1 in boosting immune defenses against mycobacteria by enhancing reactive oxygen species (ROS) production in neutrophils (PMNs). Here, we investigated the association between the rs16910526 variant and Dectin-1 expression in PMNs, as well as intracellular ROS production in response to Mtb. Furthermore, we explored the potential link between the rs16910526 gene variant and TB outcomes in Argentina. Methods DNA was extracted from blood samples obtained from a cohort of 178 TB patients and healthy subjects (HS) in Argentina. PCR amplification and sequencing were performed to identify the rs16910526 variant. Flow cytometry was utilised to assess Dectin-1 expression on the PMN plasma membrane and to measure intracellular ROS levels, as indicated by the oxidation of DHR123 in response to the Mtb antigen. Results PMNs carrying the rs16910526 variant exhibited diminished Dectin-1 expression and ROS production in response to Mtb (p < 0.0001). In a case‒control study, the rs16910526 variant had an allelic frequency of 0.112 in TB patients and 0.051 in HS. Notably, 10 out of 88 HS and 18 out of 62 TB patients harboured the variant (odds ratio [OR]: 2.55 [95% CI 1.1–5.9, p = 0.03]), indicating a potential association with TB disease. Furthermore, TB patients with the rs16910526 variant exhibited a delayed sputum smear conversion time (p < 0.004) and 100% positivity for acid-fast bacilli smears (p < 0.00001). Conclusion Our study identified a significant association between the SNP variant rs16910526 in the DECTIN-1 gene and Dectin-1 expression in the PMN, leading to altered ROS production. The higher frequency of this variant in TB patients compared to HS suggests a possible link with susceptibility to TB disease in Argentina. Graphical Abstract

show abstract

The host-pathogen-environment triad: Lessons learned through the study of the multidrug-resistant Mycobacterium tuberculosis M strain

Cited by 4 publications

References 64 publications

Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility

Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility

Untitled

Variants of human DECTIN-1 rs16910526 are linked to differential reactive oxygen species production and susceptibility to tuberculosis

Contact Info

Product

Resources

About