Immunological aspects of host–pathogen crosstalk in the co-pathogenesis of diabetes and latent tuberculosis

Verma, Arpana; Kaur, Maninder; Luthra, Princy; Singh, Lakshyaveer; Aggarwal, Divya; Verma, Indu; Radotra, Bishan Dass; Bhadada, Sanjay Kumar; Sharma, Sadhna

doi:10.3389/fcimb.2022.957512

Cited by 4 publications

(1 citation statement)

References 64 publications

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“…Verma et al established a latent TB infection mouse model and induced diabetes in Mtb-infected mice by administering streptozotocin to investigate the relationship between latent TB and diabetes. These hyperglycemic conditions led to a decrease in MCP-1 and MMP9 levels and increased MMP1 levels in latent TB infection, which may lead to reactivation of latent TB infection by disrupting granulomas (218). Clement et al reported that metabolic stress caused by hyperglycemia decreases Ag presentation ability and inhibits the proliferation of CD4 + T cells (219).…”

Section: Vaccine Application In the Context Of Underlying Diseasesmentioning

confidence: 99%

Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines

2023

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Although tuberculosis (TB) remains one of the leading causes of death from an infectious disease worldwide, the development of vaccines more effective than bacille Calmette-Guérin (BCG), the only licensed TB vaccine, has progressed slowly even in the context of the tremendous global impact of TB. Most vaccine candidates have been developed to strongly induce interferon-γ (IFN-γ)-producing T-helper type 1 (Th1) cell responses; however, accumulating evidence has suggested that other immune factors are required for optimal protection against Mycobacterium tuberculosis (Mtb) infection. In this review, we briefly describe the five hurdles that must be overcome to develop more effective TB vaccines, including those with various purposes and tested in recent promising clinical trials. In addition, we discuss the current knowledge gaps between preclinical experiments and clinical studies regarding peripheral versus tissue-specific immune responses, different underlying conditions of individuals, and newly emerging immune correlates of protection. Moreover, we propose how recently discovered TB risk or susceptibility factors can be better utilized as novel biomarkers for the evaluation of vaccine-induced protection to suggest more practical ways to develop advanced TB vaccines. Vaccines are the most effective tools for reducing mortality and morbidity from infectious diseases, and more advanced technologies and a greater understanding of host-pathogen interactions will provide feasibility and rationale for novel vaccine design and development.

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Section: Vaccine Application In the Context Of Underlying Diseasesmentioning

confidence: 99%

Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines

2023

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Impact of diabetes mellitus on tuberculosis prevention, diagnosis, and treatment from an immunologic perspective

Ye,

Li,

Yang

et al. 2024

Exploration

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The coexistence of diabetes mellitus (DM) and tuberculosis (TB) presents a significant global burden, with DM being recognized as a major risk factor for TB. This review comprehensively analyzes the immunological aspects of DM‐TB comorbidity, shedding light on the impact of DM on TB pathogenesis and immune responses. It reveals that high blood glucose levels in TB patients contribute to reduced innate immune cell count, compromised phagocytic function, and delayed antigen presentation. These factors ultimately impair the clearance of Mycobacterium tuberculosis (MTB) and delay adaptive immune responses. With the interaction between TB and DM, there is an increase in inflammation and elevated secretion of pro‐inflammatory cytokines by immune cells. This exacerbates the inflammatory response and contributes to poor treatment outcomes in TB. Moreover, the review explores the effects of DM on TB prevention, diagnosis, and treatment. It highlights how poor glycemic control, insulin resistance (IR), DM complications, and genetic factors increase the risk of MTB infection in individuals with DM. Additionally, DM‐related immune suppression adversely affects the sensitivity of traditional diagnostic tests for TB, potentially resulting in underdiagnosis and delayed intervention. To mitigate the burden of TB in DM patients, the review emphasizes the need for further research on the mechanisms underlying DM reactivation in latent TB infection (LTBI). It shows how important it is to find and treat LTBI in DM patients as soon as possible and suggests looking into biomarkers that are specific to DM to make diagnosis more accurate.

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Amoebae as training grounds for microbial pathogens

Price,

Hanford,

Al-Quadan

et al. 2024

mBio

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Grazing of amoebae on microorganisms represents one of the oldest predator-prey dynamic relationships in nature. It represents a genetic “melting pot” for an ancient and continuous multi-directional inter- and intra-kingdom horizontal gene transfer between amoebae and its preys, intracellular microbial residents, endosymbionts, and giant viruses, which has shaped the evolution, selection, and adaptation of microbes that evade degradation by predatory amoeba. Unicellular phagocytic amoebae are thought to be the ancient ancestors of macrophages with highly conserved eukaryotic processes. Selection and evolution of microbes within amoeba through their evolution to target highly conserved eukaryotic processes have facilitated the expansion of their host range to mammals, causing various infectious diseases. Legionella and environmental Chlamydia harbor an immense number of eukaryotic-like proteins that are involved in ubiquitin-related processes or are tandem repeats-containing proteins involved in protein-protein and protein-chromatin interactions. Some of these eukaryotic-like proteins exhibit novel domain architecture and novel enzymatic functions absent in mammalian cells, such as ubiquitin ligases, likely acquired from amoebae. Mammalian cells and amoebae may respond similarly to microbial factors that target highly conserved eukaryotic processes, but mammalian cells may undergo an accidental response to amoeba-adapted microbial factors. We discuss specific examples of microbes that have evolved to evade amoeba predation, including the bacterial pathogens— Legionella , Chlamydia , Coxiella, Rickettssia, Francisella, Mycobacteria , Salmonella, Bartonella , Rhodococcus , Pseudomonas, Vibrio , Helicobacter , Campylobacter , and Aliarcobacter . We also discuss the fungi Cryptococcus, and Asperigillus , as well as amoebae mimiviruses/giant viruses. We propose that amoeba-microbe interactions will continue to be a major “training ground” for the evolution, selection, adaptation, and emergence of microbial pathogens equipped with unique pathogenic tools to infect mammalian hosts. However, our progress will continue to be highly dependent on additional genomic, biochemical, and cellular data of unicellular eukaryotes.

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Immunological aspects of host–pathogen crosstalk in the co-pathogenesis of diabetes and latent tuberculosis

Cited by 4 publications

References 64 publications

Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines

Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines

Impact of diabetes mellitus on tuberculosis prevention, diagnosis, and treatment from an immunologic perspective

Amoebae as training grounds for microbial pathogens

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