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Frontiers in immunology
2022;13 1085786.

Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Gu��rin (BCG) inoculated macaques.

Edith M Walker, Kristen M Merino, Nadia Slisarenko, Brooke F Grasperge, Smriti Mehra, Chad J Roy, Deepak Kaushal, Namita Rout
Author Information
  1. Edith M Walker: Division of Microbiology at Tulane National Primate Research Center, Covington, LA, United States.
  2. Kristen M Merino: Division of Microbiology at Tulane National Primate Research Center, Covington, LA, United States.
  3. Nadia Slisarenko: Division of Microbiology at Tulane National Primate Research Center, Covington, LA, United States.
  4. Brooke F Grasperge: Division of Microbiology at Tulane National Primate Research Center, Covington, LA, United States.
  5. Smriti Mehra: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, United States.
  6. Chad J Roy: Division of Microbiology at Tulane National Primate Research Center, Covington, LA, United States.
  7. Deepak Kaushal: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, United States.
  8. Namita Rout: Division of Microbiology at Tulane National Primate Research Center, Covington, LA, United States.
PMID: 36726992 DOI: 10.3389/fimmu.2022.1085786

Abstract

Background: Although BCG vaccine protects infants from tuberculosis (TB), it has limited efficacy in adults against pulmonary TB. Further, HIV coinfection significantly increases the risk of developing active TB. In the lack of defined correlates of protection in TB disease, it is essential to explore immune responses beyond conventional CD4 T cells to gain a better understanding of the mechanisms of TB immunity.
Methods: Here, we evaluated unconventional lipid-reactive T cell responses in cynomolgus macaques following aerosol BCG inoculation and examined the impact of subsequent SIV infection on these responses. Immune responses to cellular lipids of and were examined ex vivo in peripheral blood and bronchioalveolar lavage (BAL).
Results: Prior to BCG inoculation, innate-like IFN-�� responses to mycobacterial lipids were observed in T cells. Aerosol BCG exposure induced an early increase in frequencies of BAL ����T cells, a dominant subset of lipid-reactive T cells, along with enhanced IL-7R and CXCR3 expression. Further, BCG exposure stimulated greater IFN-�� responses to mycobacterial lipids in peripheral blood and BAL, suggesting the induction of systemic and local Th1-type response in lipid-reactive T cells. Subsequent SIV infection resulted in a significant loss of IL-7R expression on blood and BAL ����T cells. Additionally, IFN-�� responses of mycobacterial lipid-reactive T cells in BAL fluid were significantly lower in SIV-infected macaques, while perforin production was maintained through chronic SIV infection.
Conclusions: Overall, these data suggest that despite SIV-induced decline in IL-7R expression and IFN-�� production by mycobacterial lipid-reactive T cells, their cytolytic potential is maintained. A deeper understanding of anti-mycobacterial lipid-reactive T cell functions may inform novel approaches to enhance TB control in individuals with or without HIV infection.

Keywords

BCG SIV lipid antigen macaque tuberculosis ����T

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Grants

  1. U42 OD024282/NIH HHS
  2. P51 OD011104/NIH HHS
  3. P20 GM103629/NIGMS NIH HHS
  4. R21 AI140840/NIAID NIH HHS
  5. U42 OD010568/NIH HHS
  6. P51 OD011133/NIH HHS
  7. R33 AI136100/NIAID NIH HHS

MeSH Term

Animals
BCG Vaccine
HIV Infections
Macaca
Respiratory Aerosols and Droplets
Mycobacterium bovis
Tuberculosis
Lipids

Chemicals

BCG Vaccine
Lipids
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 5

Word Cloud

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