Background

Chronic helminth infections typically induce an immunoregulatory environment, with markedly reduced immune responses to both parasite-specific and unrelated bystander antigens. Here we tested whether these changes are also observed in human infections with Mansonella ozzardi, a neglected filarial nematode widely distributed across Latin America.

Methods

CD4⁺ T cell populations from microfilaremic (Fil+) and uninfected (Fil-) inhabitants in M. ozzardi-endemic riverine communities in Brazil were characterized by flow cytometry analysis. Plasma concentrations of a wide range of cytokines and chemokines were measured. We examined whether M. ozzardi infection is associated with suppressed in vitro lymphoproliferative and inflammatory cytokine responses upon stimulation with filarial antigen, unrelated antigens or mitogens.

Principal findings/Conclusions

Fil+ subjects had lower plasma levels of selected inflammatory cytokines, such as TNF-α, IL-8, and IL-6, than their Fil- counterparts. However, we found no evidence for attenuated T-cell responses to filarial antigens or co-endemic pathogens, such as malaria parasites and Toxoplasma gondii. CD4⁺ T cells expressing CD39, an ectonucleosidase involved in the generation of the anti-inflammatory molecule adenosine, were increased in frequency in Fil+ subjects, compared to uninfected controls. Significantly, such an expansion was directly proportional to microfilarial loads. Surprisingly, CD39 blocking with a neutralizing antibody suppressed antigen-driven lymphoproliferation in vitro, while decreasing inflammatory cytokine responses, in Fil+ and Fil- individuals. These findings suggest that circulating CD4⁺ CD39⁺ T cells comprise subsets with both regulatory and stimulatory roles that contribute to the immune homeostasis in chronic M. ozzardi infection.

中文翻译：

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慢性蠕虫感染中的CD39和免疫调节：令人费解的曼森氏菌ozzardi病例

背景

慢性蠕虫感染通常会诱导免疫调节环境，对寄生虫特异性和无关的旁观者抗原的免疫反应明显降低。在这里，我们测试了在曼氏菌ozzardi（一种被忽略的丝状线虫，广泛分布于拉丁美洲）的人类感染中是否也观察到了这些变化。

方法

来自M.的微丝虫（Fil +）和未感染（Fil-）居民的CD4 ⁺ T细胞群体。通过流式细胞仪分析表征了巴西的ozzardi流行河沿社区。测量了多种细胞因子和趋化因子的血浆浓度。我们检查了M是否。ozzardi感染与用丝状抗原，无关抗原或有丝分裂原刺激后体外抑制的淋巴增生和炎性细胞因子反应有关。

主要发现/结论

与Fil-对应者相比，Fil +受试者的血浆中某些炎症性细胞因子（如TNF-α，IL-8和IL-6）的水平较低。但是，我们没有发现减弱的T细胞对丝状抗原或共流行病原体（例如疟原虫和弓形虫）的减毒反应的证据。与未感染的对照组相比，在Fil +受试者中表达CD39（一种参与抗炎分子腺苷生成的胞外核苷酶）的CD4 ⁺ T细胞的频率增加。值得注意的是，这种膨胀与微丝负荷成正比。令人惊讶的是，用中和抗体阻断CD39可以抑制抗原驱动的体外淋巴细胞增殖，同时降低Fil +和Fil-个人的炎症细胞因子反应。这些发现表明，循环中的CD4 ⁺ CD39 ⁺ T细胞包含具有调节作用和刺激作用的子集，有助于慢性M型小鼠的免疫稳态。ozzardi感染。