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
Emory Vaccine Center, Emory University, Atlanta, GA, United States.
Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Front Immunol. 2020 Feb 7;11:127. doi: 10.3389/fimmu.2020.00127. eCollection 2020.
(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.
结核分枝杆菌（Mtb）是一个严重的公共卫生问题，全球四分之一的人口受到感染，每年导致1000万例结核病（TB）发病和150万例死亡。有效的1型CD4 T细胞（TH1）免疫反应对于控制Mtb感染是必要的，确定调节Mtb特异性TH1免疫的因素对于更好地确定Mtb感染中保护的免疫相关因素很重要。蠕虫刺激2型（TH2）免疫反应，拮抗TH1细胞。因此，我们试图评估在肯尼亚基苏木的一组未感染艾滋病毒的成年人中，与寄生蠕虫（SM）共同感染是否会改变CD4 T细胞谱系特征。个体根据Mtb和SM感染状况分为六组：健康对照（HC）、潜伏性Mtb感染（LTBI）和活动性结核病（TB），有无SM合并感染。我们利用流式细胞术评估总CD4 T细胞以及针对Mtb抗原CFP-10和ESAT-6的CD4 T细胞的TH1/TH2功能和表型谱系状态。在所有Mtb感染组中，SM和非SM个体的总CD4 T细胞谱系特征相似。此外，在LTBI组和TB组中，SM感染均未损害Mtb特异性TH1细胞因子的产生。事实上，SM LTBI个体中IFNγ Mtb特异性CD4 T细胞的频率高于非SM LTBI个体。Mtb特异性CD4 T细胞的特征是同时表达经典的TH1标志物CXCR3和T-bet以及TH2标志物CCR4和GATA3。LTBI的SM和非SM个体之间这些标志物的表达相似。然而，与非SM TB个体相比，活动性TB的SM个体中GATA3 CCR4 TH1细胞因子Mtb特异性CD4 T细胞的频率显著更高。总之，这些数据表明，在SM感染个体中Mtb特异性TH1细胞因子的产生能力得以维持，并且Mtb特异性TH1细胞因子CD4 T细胞可以同时表达TH1和TH2标志物。在共感染常见且反复发生的高病原体负担环境中，抗原特异性CD4 T细胞反应的可塑性对于维持Mtb特异性TH1反应可能很重要。
