Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Guérin (BCG) inoculated macaques.
| Title: | Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Guérin (BCG) inoculated macaques. |
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| Authors: | Walker, Edith M., Merino, Kristen M., Slisarenko, Nadia, Grasperge, Brooke F., Mehra, Smriti, Roy, Chad J., Kaushal, Deepak, Rout, Namita |
| Source: | Frontiers in Immunology; 1/16/2023, Vol. 13, p1-15, 15p, 9 Graphs |
| 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 M. bovis and M. tuberculosis were examined ex vivo in peripheral blood and bronchioalveolar lavage (BAL). Results: Prior to BCG inoculation, innate-like IFN-γ responses to mycobacterial lipids were observed in T cells. Aerosol BCG exposure induced an early increase in frequencies of BAL γδT cells, a dominant subset of lipid-reactive T cells, along with enhanced IL-7R and CXCR3 expression. Further, BCG exposure stimulated greater IFN-γ 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 γδT cells. Additionally, IFN-γ 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-γ 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. [ABSTRACT FROM AUTHOR] |
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| Database: | Complementary Index |
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| Items | – Name: Title Label: Title Group: Ti Data: Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Guérin (BCG) inoculated macaques. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Walker%2C+Edith+M%2E%22">Walker, Edith M.</searchLink><br /><searchLink fieldCode="AR" term="%22Merino%2C+Kristen+M%2E%22">Merino, Kristen M.</searchLink><br /><searchLink fieldCode="AR" term="%22Slisarenko%2C+Nadia%22">Slisarenko, Nadia</searchLink><br /><searchLink fieldCode="AR" term="%22Grasperge%2C+Brooke+F%2E%22">Grasperge, Brooke F.</searchLink><br /><searchLink fieldCode="AR" term="%22Mehra%2C+Smriti%22">Mehra, Smriti</searchLink><br /><searchLink fieldCode="AR" term="%22Roy%2C+Chad+J%2E%22">Roy, Chad J.</searchLink><br /><searchLink fieldCode="AR" term="%22Kaushal%2C+Deepak%22">Kaushal, Deepak</searchLink><br /><searchLink fieldCode="AR" term="%22Rout%2C+Namita%22">Rout, Namita</searchLink> – Name: TitleSource Label: Source Group: Src Data: Frontiers in Immunology; 1/16/2023, Vol. 13, p1-15, 15p, 9 Graphs – Name: Abstract Label: Abstract Group: Ab Data: 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 M. bovis and M. tuberculosis were examined ex vivo in peripheral blood and bronchioalveolar lavage (BAL). Results: Prior to BCG inoculation, innate-like IFN-γ responses to mycobacterial lipids were observed in T cells. Aerosol BCG exposure induced an early increase in frequencies of BAL γδT cells, a dominant subset of lipid-reactive T cells, along with enhanced IL-7R and CXCR3 expression. Further, BCG exposure stimulated greater IFN-γ 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 γδT cells. Additionally, IFN-γ 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-γ 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. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3389/fimmu.2022.1085786 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 15 StartPage: 1 Titles: – TitleFull: Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Guérin (BCG) inoculated macaques. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Walker, Edith M. – PersonEntity: Name: NameFull: Merino, Kristen M. – PersonEntity: Name: NameFull: Slisarenko, Nadia – PersonEntity: Name: NameFull: Grasperge, Brooke F. – PersonEntity: Name: NameFull: Mehra, Smriti – PersonEntity: Name: NameFull: Roy, Chad J. – PersonEntity: Name: NameFull: Kaushal, Deepak – PersonEntity: Name: NameFull: Rout, Namita IsPartOfRelationships: – BibEntity: Dates: – D: 16 M: 01 Text: 1/16/2023 Type: published Y: 2023 Identifiers: – Type: issn-print Value: 16643224 Numbering: – Type: volume Value: 13 Titles: – TitleFull: Frontiers in Immunology Type: main |
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