CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses.
In: Frontiers in Immunology, 2020-02-07, S. 1-17
Online
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
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CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses.
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Autor/in / Beteiligte Person: | McLaughlin, Taryn A. ; Khayumbi, Jeremiah ; Ongalo, Joshua ; Tonui, Joan ; Campbell, Angela ; Allana, Salim ; Gurrion Ouma, Samuel ; Odhiambo, Felix Hayara ; Gandhi, Neel R. ; Day, Cheryl L. |
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Zeitschrift: | Frontiers in Immunology, 2020-02-07, S. 1-17 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
ISSN: | 1664-3224 (print) |
DOI: | 10.3389/fimmu.2020.00127 |
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