CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses
Mycobacterium tuberculosis (Mtb) is a serious public health concern, infecting a quarter of the world and leading to 10 million cases of tuberculosis (TB) disease and 1. 5 million deaths annually. An effective type 1 CD4 T cell (TH1) immune response is necessary to control Mtb infection and defining...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00127/full |
| _version_ | 1828399735098048512 |
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| author | Taryn A. McLaughlin Jeremiah Khayumbi Joshua Ongalo Joan Tonui Angela Campbell Salim Allana Samuel Gurrion Ouma Felix Hayara Odhiambo Neel R. Gandhi Neel R. Gandhi Cheryl L. Day Cheryl L. Day |
| author_facet | Taryn A. McLaughlin Jeremiah Khayumbi Joshua Ongalo Joan Tonui Angela Campbell Salim Allana Samuel Gurrion Ouma Felix Hayara Odhiambo Neel R. Gandhi Neel R. Gandhi Cheryl L. Day Cheryl L. Day |
| author_sort | Taryn A. McLaughlin |
| collection | DOAJ |
| description | Mycobacterium tuberculosis (Mtb) is a serious public health concern, infecting a quarter of the world and leading to 10 million cases of tuberculosis (TB) disease and 1. 5 million deaths annually. An effective type 1 CD4 T cell (TH1) immune response is necessary to control Mtb infection and defining factors that modulate Mtb-specific TH1 immunity is important to better define immune correlates of protection in Mtb infection. Helminths stimulate type 2 (TH2) immune responses, which antagonize TH1 cells. As such, we sought to evaluate whether co-infection with the parasitic helminth Schistosoma mansoni (SM) modifies CD4 T cell lineage profiles in a cohort of HIV-uninfected adults in Kisumu, Kenya. Individuals were categorized into six groups by Mtb and SM infection status: healthy controls (HC), latent Mtb infection (LTBI) and active tuberculosis (TB), with or without concomitant SM infection. We utilized flow cytometry to evaluate the TH1/TH2 functional and phenotypic lineage state of total CD4 T cells, as well as CD4 T cells specific for the Mtb antigens CFP-10 and ESAT-6. Total CD4 T cell lineage profiles were similar between SM+ and SM− individuals in all Mtb infection groups. Furthermore, in both LTBI and TB groups, SM infection did not impair Mtb-specific TH1 cytokine production. In fact, SM+ LTBI individuals had higher frequencies of IFNγ+ Mtb-specific CD4 T cells than SM− LTBI individuals. Mtb-specific CD4 T cells were characterized by expression of both classical TH1 markers, CXCR3 and T-bet, and TH2 markers, CCR4, and GATA3. The expression of these markers was similar between SM+ and SM− individuals with LTBI. However, SM+ individuals with active TB had significantly higher frequencies of GATA3+ CCR4+ TH1 cytokine+ Mtb-specific CD4 T cells, compared with SM− TB individuals. Together, these data indicate that Mtb-specific TH1 cytokine production capacity is maintained in SM-infected individuals, and that Mtb-specific TH1 cytokine+ CD4 T cells can express both TH1 and TH2 markers. In high pathogen burden settings where co-infection is common and reoccurring, plasticity of antigen-specific CD4 T cell responses may be important in preserving Mtb-specific TH1 responses. |
| first_indexed | 2024-12-10T09:21:43Z |
| format | Article |
| id | doaj.art-e850b989644a48bfb1678ab9e55a4d71 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T09:21:43Z |
| publishDate | 2020-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e850b989644a48bfb1678ab9e55a4d712022-12-22T01:54:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011110.3389/fimmu.2020.00127513846CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 ResponsesTaryn A. McLaughlin0Jeremiah Khayumbi1Joshua Ongalo2Joan Tonui3Angela Campbell4Salim Allana5Samuel Gurrion Ouma6Felix Hayara Odhiambo7Neel R. Gandhi8Neel R. Gandhi9Cheryl L. Day10Cheryl L. Day11Emory Vaccine Center, Emory University, Atlanta, GA, United StatesCenter for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaCenter for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaCenter for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United StatesDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United StatesCenter for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaCenter for Global Health Research, Kenya Medical Research Institute, Kisumu, KenyaDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United StatesDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, United StatesEmory Vaccine Center, Emory University, Atlanta, GA, United StatesDepartment of Microbiology & Immunology, Emory University School of Medicine, Atlanta, GA, United StatesMycobacterium tuberculosis (Mtb) is a serious public health concern, infecting a quarter of the world and leading to 10 million cases of tuberculosis (TB) disease and 1. 5 million deaths annually. An effective type 1 CD4 T cell (TH1) immune response is necessary to control Mtb infection and defining factors that modulate Mtb-specific TH1 immunity is important to better define immune correlates of protection in Mtb infection. Helminths stimulate type 2 (TH2) immune responses, which antagonize TH1 cells. As such, we sought to evaluate whether co-infection with the parasitic helminth Schistosoma mansoni (SM) modifies CD4 T cell lineage profiles in a cohort of HIV-uninfected adults in Kisumu, Kenya. Individuals were categorized into six groups by Mtb and SM infection status: healthy controls (HC), latent Mtb infection (LTBI) and active tuberculosis (TB), with or without concomitant SM infection. We utilized flow cytometry to evaluate the TH1/TH2 functional and phenotypic lineage state of total CD4 T cells, as well as CD4 T cells specific for the Mtb antigens CFP-10 and ESAT-6. Total CD4 T cell lineage profiles were similar between SM+ and SM− individuals in all Mtb infection groups. Furthermore, in both LTBI and TB groups, SM infection did not impair Mtb-specific TH1 cytokine production. In fact, SM+ LTBI individuals had higher frequencies of IFNγ+ Mtb-specific CD4 T cells than SM− LTBI individuals. Mtb-specific CD4 T cells were characterized by expression of both classical TH1 markers, CXCR3 and T-bet, and TH2 markers, CCR4, and GATA3. The expression of these markers was similar between SM+ and SM− individuals with LTBI. However, SM+ individuals with active TB had significantly higher frequencies of GATA3+ CCR4+ TH1 cytokine+ Mtb-specific CD4 T cells, compared with SM− TB individuals. Together, these data indicate that Mtb-specific TH1 cytokine production capacity is maintained in SM-infected individuals, and that Mtb-specific TH1 cytokine+ CD4 T cells can express both TH1 and TH2 markers. In high pathogen burden settings where co-infection is common and reoccurring, plasticity of antigen-specific CD4 T cell responses may be important in preserving Mtb-specific TH1 responses.https://www.frontiersin.org/article/10.3389/fimmu.2020.00127/fullhelminthSchistosoma mansoniMycobacterium tuberculosisLTBIactive TB diseaseCD4 T cell |
| spellingShingle | Taryn A. McLaughlin Jeremiah Khayumbi Joshua Ongalo Joan Tonui Angela Campbell Salim Allana Samuel Gurrion Ouma Felix Hayara Odhiambo Neel R. Gandhi Neel R. Gandhi Cheryl L. Day Cheryl L. Day CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses Frontiers in Immunology helminth Schistosoma mansoni Mycobacterium tuberculosis LTBI active TB disease CD4 T cell |
| title | CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses |
| title_full | CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses |
| title_fullStr | CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses |
| title_full_unstemmed | CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses |
| title_short | CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses |
| title_sort | cd4 t cells in mycobacterium tuberculosis and schistosoma mansoni co infected individuals maintain functional th1 responses |
| topic | helminth Schistosoma mansoni Mycobacterium tuberculosis LTBI active TB disease CD4 T cell |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00127/full |
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