Characterization of <i>Mycobacterium tuberculosis</i>–Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection

Makatsa, Mohau; Omondi, Millicent A.; Bunjun, Rubina; Wilkinson, Robert J.; Riou, Catherine; Burgers, Wendy A.

doi:10.4049/jimmunol.2200140

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…In contrast to the SAS-formulated candidate, Pal-CGHP induced significant IL-22 production but no IL-17 response. Recently, IL-22 was suggested to be associated with protection during TB infection, − while IL-10 was proposed to modulate the Th1 proinflammatory immune response and prevent potentially harmful effects of an excessive immune response. The high levels of IL-10 observed in this study may be related to the strong IFNγ response …”

Section: Resultsmentioning

confidence: 99%

Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection

Bellini,

Vergara,

Bencs

et al. 2023

Bioconjugate Chem.

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The complex immunopathology ofMycobacterium tuberculosis(Mtb) is one of the main challenges in developing a novel vaccine against this pathogen, particularly regarding eliciting protection against both active and latent stages. Multistage vaccines, which contain antigens expressed in both phases, represent a promising strategy for addressing this issue, as testified by the tuberculosis vaccine clinical pipeline. Given this approach, we designed and characterized a multistage peptide-based vaccine platform containing CD4+ and CD8+ T cell epitopes previously validated for inducing a relevant T cell response against Mtb. After preliminary screening, CFP10 (32−39), GlfT2 (4−12), HBHA (185−194), and PPE15 (1−15) were selected as promising candidates, and we proved that the PM1 pool of these peptides triggered a T cell response in Mtb-sensitized human peripheral blood mononuclear cells (PBMCs). Taking advantage of the use of thiol-maleimide chemoselective ligation, we synthesized a multiepitope conjugate (Ac-CGHP). Our results showed a structure−activity relationship between the conjugation and a higher tendency to fold and assume an ordered secondary structure. Moreover, the palmitoylated conjugate (Pal-CGHP) comprising the same peptide antigens was associated with an enhanced cellular uptake in human and murine antigen-presenting cells and a better immunogenicity profile. Immunization study, conducted in BALB/c mice, showed that Pal-CGHP induced a significantly higher T cell proliferation and production of IFNγ and TNFα over PM1 formulated in the Sigma Adjuvant System.

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Section: Resultsmentioning

confidence: 99%

Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection

Bellini,

Vergara,

Bencs

et al. 2023

Bioconjugate Chem.

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Mycobacterium potentiates protection from colorectal cancer by gut microbial alterations

et al. 2022

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Not only are many Mycobacteria pathogens, but they can act as strong non‐specific immunopotentiators, generating beneficial effects on the pathogenesis of some diseases. However, there has been no direct evidence of the effect of mycobacterial species on colorectal cancer (CRC). Herein, we showed that there may be a meaningful inverse correlation between the incidence of tuberculosis and CRC based on global statistics and that heat‐killed Mycobacterial tuberculosis and live Mycobacterium bovis (Bacillus Calmette–Guérin strain) could ameliorate CRC development. In particular, using a faecal microbiota transplantation and a comparison between separate housing and cohousing, we demonstrated that the gut microbiota is involved in the protective effects. The microbial alterations can be elucidated by the modulation of antimicrobial activities including those of the Reg3 family genes. Furthermore, interleukin‐22 production by T helper cells contributed to the anti‐inflammatory activity of Mycobacteria. Our results revealed a novel role of Mycobacteria involving gut microbial alterations in dampening inflammation‐associated CRC and an immunological mechanism underlying the interaction between microbes and host immunity.

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T Cell Responses during Human Immunodeficiency Virus/Mycobacterium tuberculosis Coinfection

Bohórquez,

Jagannath,

et al. 2024

Vaccines

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Coinfection with Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) is a significant public health concern. Individuals infected with Mtb who acquire HIV are approximately 16 times more likely to develop active tuberculosis. T cells play an important role as both targets for HIV infection and mediators of the immune response against both pathogens. This review aims to synthesize the current literature and provide insights into the effects of HIV/Mtb coinfection on T cell populations and their contributions to immunity. Evidence from multiple in vitro and in vivo studies demonstrates that T helper responses are severely compromised during coinfection, leading to impaired cytotoxic responses. Moreover, HIV’s targeting of Mtb-specific cells, including those within granulomas, offers an explanation for the severe progression of the disease. Herein, we discuss the patterns of differentiation, exhaustion, and transcriptomic changes in T cells during coinfection, as well as the metabolic adaptations that are necessary for T cell maintenance and functionality. This review highlights the interconnectedness of the immune response and the pathogenesis of HIV/Mtb coinfection.

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Characterization of Mycobacterium tuberculosis–Specific Th22 Cells and the Effect of Tuberculosis Disease and HIV Coinfection

Cited by 3 publications

References 58 publications

Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection

Design and Characterization of a Multistage Peptide-Based Vaccine Platform to Target Mycobacterium tuberculosis Infection

Mycobacterium potentiates protection from colorectal cancer by gut microbial alterations

T Cell Responses during Human Immunodeficiency Virus/Mycobacterium tuberculosis Coinfection

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