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Pathogens
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Understanding the Immune Response during HIV and Mycobacterium tuberculosis (Mtb)...
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Understanding the Immune Response during HIV and Mycobacterium tuberculosis (Mtb) Infection

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Immunological Responses and Immune Defense Mechanisms".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 5857

Special Issue Editors

Dr. Namita Rout

E-Mail Website
Guest Editor
Division of Microbiology, Tulane National Primate Research Center, Tulane University, Covington, LA 70433, USA
Interests: HIV pathogenesis and cure; HIV/TB coinfection; aging mucosal immunity and inflammation of aging
Special Issues, Collections and Topics in MDPI journals
Dr. Vijayakumar Velu

E-Mail Website
Guest Editor
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA
Interests: HIV; SIV; tuberculosis; viral hepatitis; vaccine; immunology; pathogenesis

Special Issue Information

Dear Colleagues,

Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb) remain leading causes of mortality and morbidity in infected people. HIV-Mtb coinfection further increases the risk of tuberculosis (TB) by 20-fold and mortality by 4-fold, while altering the clinical presentation and outcome. Moreover, it complicates TB diagnosis and treatment even in individuals on antiretroviral therapy (ART).

Although HIV-1-induced depletion of CD4+ T cells underlies worse outcome of HIV-TB coinfection, broader immune deficits induced by HIV also contribute to disease pathogenesis. Conversely, Mtb infection also impacts on the immune response to HIV-1 by driving transcriptional activation via production of inflammatory cytokines/chemokines and increasing cellular susceptibility to HIV-1 infection via increased CCR5 expression and production of cytokines (such as IL-2 and Toll-like receptor 2 upregulation). Yet, precise immunopathological mechanisms of HIV-TB coinfection remain unclear. While these impairments in immune responses are a major barrier to properly diagnosing or ameliorating TB, they also represent an opportunity to understand novel immune mechanisms of protection against TB in HIV-infected and uninfected persons.

Additionally, there is emerging interest in understanding innate immune responses to Mtb and BCG vaccines in HIV-infected individuals and developing TB/HIV dual vaccine candidates. Improved understanding of the immunopathology of HIV-associated TB has the potential to improve preventative measures, such as by informing vaccine design and diagnostics and developing new immunomodulatory therapies. This Special Issue aims to provide a comprehensive overview of our current understanding of the immune response during HIV and Mtb infection. We therefore welcome the submission of original research and review articles that cover, but are not limited to, the following topics:

  1. Identification of biomarkers of HIV/TB coinfection.
  2. Changes in immune cells functions and signaling pathways that increase TB susceptibility in coinfected individuals or in animal models of HIV/TB.
  3. Role of innate and adaptive immune cells in response to Mtb/BCG at lung mucosa.
  4. Effects of ART on lung mucosal immune responses to BCG vaccine and Mtb infection.

Dr. Namita Rout
Dr. Vijayakumar Velu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Mycobacterium tuberculosis
  • HIV
  • SIV
  • ART
  • BCG
  • tuberculosis
  • lung mucosa
  • immune response
  • pathogenesis

Published Papers (3 papers)

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Research

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18 pages, 8090 KiB  
Article
Natural Killer Repertoire Restoration in TB/HIV Co-Infected Individuals Experienced an Immune Reconstitution Syndrome (CAMELIA Trial, ANRS 12153)
by Polidy Pean, Yoann Madec, Eric Nerrienet, Laurence Borand, Didier Laureillard, Marcelo Fernandez, Olivier Marcy and Daniel Scott-Algara
Pathogens 2023, 12(10), 1241; https://doi.org/10.3390/pathogens12101241 - 13 Oct 2023
Viewed by 968
Abstract
IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. [...] Read more.
IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm3) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals. Full article
(This article belongs to the Special Issue Understanding the Immune Response during HIV and Mycobacterium tuberculosis (Mtb) Infection)
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Review

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13 pages, 775 KiB  
Review
Immune Responses in Lung Granulomas during Mtb/HIV Co-Infection: Implications for Pathogenesis and Therapy
by Deepak Kaushal, Dhiraj K. Singh and Smriti Mehra
Pathogens 2023, 12(9), 1120; https://doi.org/10.3390/pathogens12091120 - 01 Sep 2023
Cited by 1 | Viewed by 1130
Abstract
HIV and TB are the cause of significant worldwide mortality and pose a grave danger to the global public health. TB is the leading cause of death in HIV-infected persons, with one in four deaths attributable to TB. While the majority of healthy [...] Read more.
HIV and TB are the cause of significant worldwide mortality and pose a grave danger to the global public health. TB is the leading cause of death in HIV-infected persons, with one in four deaths attributable to TB. While the majority of healthy individuals infected with M. tuberculosis (Mtb) are able to control the infection, co-infection with HIV increases the risk of TB infection progressing to TB disease by over 20-fold. While antiretroviral therapy (ART), the cornerstone of HIV care, decreases the incidence of TB in HIV-uninfected people, this remains 4- to 7-fold higher after ART in HIV-co-infected individuals in TB-endemic settings, regardless of the duration of therapy. Thus, the immune control of Mtb infection in Mtb/HIV-co-infected individuals is not fully restored by ART. We do not fully understand the reasons why Mtb/HIV-co-infected individuals maintain a high susceptibility to the reactivation of LTBI, despite an effective viral control by ART. A deep understanding of the molecular mechanisms that govern HIV-induced reactivation of TB is essential to develop improved treatments and vaccines for the Mtb/HIV-co-infected population. We discuss potential strategies for the mitigation of the observed chronic immune activation in combination with both anti-TB and anti-retroviral approaches. Full article
(This article belongs to the Special Issue Understanding the Immune Response during HIV and Mycobacterium tuberculosis (Mtb) Infection)
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16 pages, 1186 KiB  
Review
Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome—An Extempore Game of Misfiring with Defense Arsenals
by Ramachandran Vignesh, Pachamuthu Balakrishnan, Hong Yien Tan, Yean Kong Yong, Vijayakumar Velu, Marie Larsson and Esaki M. Shankar
Pathogens 2023, 12(2), 210; https://doi.org/10.3390/pathogens12020210 - 29 Jan 2023
Cited by 3 | Viewed by 3287
Abstract
The lethal combination involving TB and HIV, known as “syndemic” diseases, synergistically act upon one another to magnify the disease burden. Individuals on anti-retroviral therapy (ART) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the [...] Read more.
The lethal combination involving TB and HIV, known as “syndemic” diseases, synergistically act upon one another to magnify the disease burden. Individuals on anti-retroviral therapy (ART) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART, eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although a significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic marker still remain a grey area of investigation. Here, we reviewed the latest research developments into IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS. Full article
(This article belongs to the Special Issue Understanding the Immune Response during HIV and Mycobacterium tuberculosis (Mtb) Infection)
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