A CD4+ TNF+ monofunctional memory T-cell response to BCG vaccination is associated with Mycobacterium tuberculosis infection in infants exposed to HIV

Warr, Alex J; Anterasian, Christine; Shah, Javeed A.; Rosa, Stephen C. De; Nguyen, Felicia K.; Maleche‐Obimbo, Elizabeth; Cranmer, Lisa M; Matemo, Daniel; Mecha, Jerphason; Kinuthia, John; LaCourse, Sylvia M; John‐Stewart, Grace; Hawn, Thomas R.

doi:10.1016/j.ebiom.2022.104023

Cited by 5 publications

(3 citation statements)

References 30 publications

(42 reference statements)

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“…In addition, lipid extracts from both BCG and Mtb strains prompted higher and lower frequencies of effector and central memory T cells, respectively. In particular, effector memory cells are induced by BCG vaccination in humans and represent the predominant cell population in the lungs of vaccinated mice, which has been associated with stronger and more efficient protection against infection ( 29 – 32 ). Conversely, smaller populations of central memory T cells result in poorer memory responses ( 33 – 36 ).…”

Section: Discussionmentioning

confidence: 99%

Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract

Sarno,

Leite,

Augusto

et al. 2024

Front. Immunol.

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IntroductionThe attenuation of BCG has led to the loss of not only immunogenic proteins but also lipid antigens.MethodsThus, we compared the macrophage and T-cell responses to nonpolar lipid extracts harvested from BCG and Mycobacterium tuberculosis (Mtb) to better understand the role of BCG lipids in the already known diminished responses of the vaccine strain.ResultsRelative to Mtb, nonpolar lipid extract from BCG presented a reduced capacity to trigger the expression of the genes encoding TNF, IL-1b, IL-6 and IL-10 in RAW 264.7 macrophages. Immunophenotyping of PBMCs isolated from healthy individuals revealed that lipids from both BCG and Mtb were able to induce an increased frequency of CD4+ and CD8+ T cells, but only the lipid extract from Mtb enhanced the frequency of CD4-CD8-double-negative, γσ+, CD4+HLA-DR+, and γσ+HLA-DR+ T cells relative to the nonstimulated control. Interestingly, only the Mtb lipid extract was able to increase the frequency of CD4+ memory (CD45RO+) T cells, whereas the BCG lipid extract induced a diminished frequency of CD4+ central memory (CD45RO+CCR7-) T cells after 48 h of culture compared to Mtb.DiscussionThese findings show that the nonpolar lipids of the BCG bacilli presented diminished ability to trigger both proinflammatory and memory responses and suggest a potential use of Mtb lipids as adjuvants to increase the BCG vaccine efficacy.

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Section: Discussionmentioning

confidence: 99%

Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract

Sarno,

Leite,

Augusto

et al. 2024

Front. Immunol.

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show abstract

“…Despite being inexpensive, TST is not recommended for Mtb in patients with HIV/TB co‐infection, because host immunosuppression state can yield false‐negative results (Table 1). Immmunocompromised people such as patients with AIDS are at a higher risk of TST anergy due to decreased CD4 + T cell count and impaired T‐cell function [4]. Another alternative immunological test used for auxiliary TB diagnosis, the Interferon gamma (IFN‐γ) release assays (IGRAs), shows higher specificity than TST in BCG unvaccinated individuals (88% vs. 70%) [13].…”

Section: Challenges Of Traditional Techniques For Diagnosing Tb In Pa...mentioning

confidence: 99%

“…TB is a serious global health problem: in 2021, an estimated 10.6 million people were infected with TB, and 187 000 people living with HIV (PLWH) died of tuberculosis [3]. The main reasons why these two pathogens increase disease susceptibility and accelerate health deterioration are that: (a) the progressive immunodeficiency that occurs in HIV-infected individuals suppresses the T cell response to Mtb [4]. (b) Mtb promotes HIV replication and infection by increasing the expression of the viral coreceptor C-C chemokine receptor type 5 (CCR5) [5].…”

Section: Introductionmentioning

confidence: 99%

Bottlenecks and recent advancements in detecting Mycobacterium tuberculosis in patients with HIV

Lin

Sun

Wang

et al. 2023

iLABMED

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Tuberculosis (TB) remains a leading cause of deaths among patients with acquired immunodeficiency syndrome patients. Early diagnosis of TB is essential for administering timely anti-TB therapy and improving health outcomes, particularly in the people living with HIV. However, conventional techniques used to detect Mycobacterium tuberculosis have significant drawbacks: for example, sputum smear microscopy has low sensitivity, and liquid culture is time-consuming in patients with HIV-TB co-infection due to low sputum production. In addition, while immunological-based methods involving tuberculin skin testing and interferon gamma release assays are commonly used for auxiliary TB diagnosis, they are often inaccurate in immunodeficient patients. Molecular techniques such as line probe assays,

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Advances in technology for the laboratory diagnosis of individuals with HIV/AIDS coinfected with Mycobacterium tuberculosis

Sun,

Han,

Yan

et al. 2024

Biosafety and Health

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A CD4+ TNF+ monofunctional memory T-cell response to BCG vaccination is associated with Mycobacterium tuberculosis infection in infants exposed to HIV

Cited by 5 publications

References 30 publications

Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract

Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract

Bottlenecks and recent advancements in detecting Mycobacterium tuberculosis in patients with HIV

Advances in technology for the laboratory diagnosis of individuals with HIV/AIDS coinfected with Mycobacterium tuberculosis

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