Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses
IntroductionThe rising global burden of metabolic disease impacts the control of endemic tuberculosis (TB) in many regions, as persons with diabetes mellitus (DM) are up to three times more likely to develop active TB than those without DM. Active TB can also promote glucose intolerance during both...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151528/full |
| _version_ | 1827939521837137920 |
|---|---|
| author | Robert Krause Robert Krause Christian M. Warren Joshua D. Simmons Peter F. Rebeiro Peter F. Rebeiro Peter F. Rebeiro Fernanda Maruri Fernanda Maruri Farina Karim Farina Karim Farina Karim Timothy R. Sterling Timothy R. Sterling John R. Koethe Al Leslie Al Leslie Al Leslie Yuri F. van der Heijden Yuri F. van der Heijden Yuri F. van der Heijden |
| author_facet | Robert Krause Robert Krause Christian M. Warren Joshua D. Simmons Peter F. Rebeiro Peter F. Rebeiro Peter F. Rebeiro Fernanda Maruri Fernanda Maruri Farina Karim Farina Karim Farina Karim Timothy R. Sterling Timothy R. Sterling John R. Koethe Al Leslie Al Leslie Al Leslie Yuri F. van der Heijden Yuri F. van der Heijden Yuri F. van der Heijden |
| author_sort | Robert Krause |
| collection | DOAJ |
| description | IntroductionThe rising global burden of metabolic disease impacts the control of endemic tuberculosis (TB) in many regions, as persons with diabetes mellitus (DM) are up to three times more likely to develop active TB than those without DM. Active TB can also promote glucose intolerance during both acute infection and over a longer term, potentially driven by aspects of the immune response. Identifying patients likely to have persistent hyperglycemia following TB treatment would enable closer monitoring and care, and an improved understanding of underlying immunometabolic dysregulation.MethodsWe measured the relationship of plasma cytokine levels, T cell phenotypes and functional responses with the change in hemoglobin A1c (HbA1c) before and after treatment of pulmonary TB in a prospective observational cohort in Durban, South Africa. Participants were stratified based on stable/increased HbA1c (n = 16) versus decreased HbA1c (n = 46) levels from treatment initiation to 12 month follow-up.ResultsCD62 P-selectin was up- (1.5-fold) and IL-10 downregulated (0.85-fold) in plasma among individuals whose HbA1c remained stable/increased during TB treatment. This was accompanied by increased pro-inflammatory TB-specific IL-17 production (Th17). In addition, Th1 responses were upregulated in this group, including TNF-α production and CX3CR1 expression, with decreased IL-4 and IL-13 production. Finally, the TNF-α+ IFNγ+ CD8+ T cells were associated with stable/increased HbA1c. These changes were all significantly different in the stable/increased HbA1c relative to the decreased HbA1c group.DiscussionOverall, these data suggest that patients with stable/increased HbA1c had an increased pro-inflammatory state. Persistent inflammation and elevated T cell activity in individuals with unresolved dysglycemia following TB treatment may indicate failure to fully resolve infection or may promote persistent dysglycemia in these individuals, and further studies are needed to explore potential mechanisms. |
| first_indexed | 2024-03-13T08:54:45Z |
| format | Article |
| id | doaj.art-e3d677862bc44747b7d9def73f26d451 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T08:54:45Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e3d677862bc44747b7d9def73f26d4512023-05-29T04:15:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11515281151528Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responsesRobert Krause0Robert Krause1Christian M. Warren2Joshua D. Simmons3Peter F. Rebeiro4Peter F. Rebeiro5Peter F. Rebeiro6Fernanda Maruri7Fernanda Maruri8Farina Karim9Farina Karim10Farina Karim11Timothy R. Sterling12Timothy R. Sterling13John R. Koethe14Al Leslie15Al Leslie16Al Leslie17Yuri F. van der Heijden18Yuri F. van der Heijden19Yuri F. van der Heijden20Africa Health Research Institute (AHRI), Durban, South AfricaCollege of Health Sciences, School of Laboratory Medicine & Medical Sciences, University of KwaZulu Natal, Durban, South AfricaDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesDepartment of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, United StatesVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesAfrica Health Research Institute (AHRI), Durban, South AfricaCollege of Health Sciences, School of Laboratory Medicine & Medical Sciences, University of KwaZulu Natal, Durban, South AfricaVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesAfrica Health Research Institute (AHRI), Durban, South AfricaCollege of Health Sciences, School of Laboratory Medicine & Medical Sciences, University of KwaZulu Natal, Durban, South AfricaDivision of Infection and Immunity, University College London, London, United KingdomDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesVanderbilt Tuberculosis Center, Vanderbilt University School of Medicine, Nashville, TN, United StatesThe Aurum Institute, Johannesburg, South AfricaIntroductionThe rising global burden of metabolic disease impacts the control of endemic tuberculosis (TB) in many regions, as persons with diabetes mellitus (DM) are up to three times more likely to develop active TB than those without DM. Active TB can also promote glucose intolerance during both acute infection and over a longer term, potentially driven by aspects of the immune response. Identifying patients likely to have persistent hyperglycemia following TB treatment would enable closer monitoring and care, and an improved understanding of underlying immunometabolic dysregulation.MethodsWe measured the relationship of plasma cytokine levels, T cell phenotypes and functional responses with the change in hemoglobin A1c (HbA1c) before and after treatment of pulmonary TB in a prospective observational cohort in Durban, South Africa. Participants were stratified based on stable/increased HbA1c (n = 16) versus decreased HbA1c (n = 46) levels from treatment initiation to 12 month follow-up.ResultsCD62 P-selectin was up- (1.5-fold) and IL-10 downregulated (0.85-fold) in plasma among individuals whose HbA1c remained stable/increased during TB treatment. This was accompanied by increased pro-inflammatory TB-specific IL-17 production (Th17). In addition, Th1 responses were upregulated in this group, including TNF-α production and CX3CR1 expression, with decreased IL-4 and IL-13 production. Finally, the TNF-α+ IFNγ+ CD8+ T cells were associated with stable/increased HbA1c. These changes were all significantly different in the stable/increased HbA1c relative to the decreased HbA1c group.DiscussionOverall, these data suggest that patients with stable/increased HbA1c had an increased pro-inflammatory state. Persistent inflammation and elevated T cell activity in individuals with unresolved dysglycemia following TB treatment may indicate failure to fully resolve infection or may promote persistent dysglycemia in these individuals, and further studies are needed to explore potential mechanisms.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151528/fullhyperglycemiatuberculosisdiabetesHIVHbA1cIL-17 |
| spellingShingle | Robert Krause Robert Krause Christian M. Warren Joshua D. Simmons Peter F. Rebeiro Peter F. Rebeiro Peter F. Rebeiro Fernanda Maruri Fernanda Maruri Farina Karim Farina Karim Farina Karim Timothy R. Sterling Timothy R. Sterling John R. Koethe Al Leslie Al Leslie Al Leslie Yuri F. van der Heijden Yuri F. van der Heijden Yuri F. van der Heijden Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses Frontiers in Immunology hyperglycemia tuberculosis diabetes HIV HbA1c IL-17 |
| title | Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses |
| title_full | Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses |
| title_fullStr | Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses |
| title_full_unstemmed | Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses |
| title_short | Failure to decrease HbA1c levels following TB treatment is associated with elevated Th1/Th17 CD4+ responses |
| title_sort | failure to decrease hba1c levels following tb treatment is associated with elevated th1 th17 cd4 responses |
| topic | hyperglycemia tuberculosis diabetes HIV HbA1c IL-17 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1151528/full |
| work_keys_str_mv | AT robertkrause failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT robertkrause failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT christianmwarren failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT joshuadsimmons failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT peterfrebeiro failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT peterfrebeiro failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT peterfrebeiro failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT fernandamaruri failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT fernandamaruri failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT farinakarim failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT farinakarim failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT farinakarim failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT timothyrsterling failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT timothyrsterling failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT johnrkoethe failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT alleslie failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT alleslie failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT alleslie failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT yurifvanderheijden failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT yurifvanderheijden failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses AT yurifvanderheijden failuretodecreasehba1clevelsfollowingtbtreatmentisassociatedwithelevatedth1th17cd4responses |