CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses

• Published in: Frontiers in immunology Vol. 11; p. 127
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.02.2020
• Subjects: active TB disease; Adult; CD4 T cell; CD4-Positive T-Lymphocytes - immunology; Coinfection - immunology; Female; helminth; Humans; Immunology; Kenya; Latent Tuberculosis - immunology; LTBI; Male; Middle Aged; Mycobacterium tuberculosis; Schistosoma mansoni; Schistosomiasis mansoni - immunology; Th1 Cells - immunology; Th2 Cells - immunology; Tuberculosis - immunology; Young Adult; Kenya; Schistosoma mansoni; Mycobacterium tuberculosis; CD4 T cell; active TB disease; helminth; LTBI; TH1; TH2
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.00127

(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 (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.