Scorza Breanna M, Pessôa-Pereira Danielle, Pabon-Rodriguez Felix, Beasley Erin A, Mahachi Kurayi, Cox Arin D, Kontowicz Eric, Baccam Tyler, Wilson Geneva, Waugh Max C, Vollmer Shelbe, Toepp Angela, Raju Kavya, Chigbo Ogechukwu C, Elliff Jonah, Becker Greta, Cyndari Karen I, Tang Serena, Brown Grant, Petersen Christine A
Department of Epidemiology, University of Iowa, Iowa City, Iowa, USA.
Department of Biostatistics & Health Data Science, Indiana University, Indianapolis, Indiana, USA.
Infect Immun. 2025 Sep 9;93(9):e0018225. doi: 10.1128/iai.00182-25. Epub 2025 Jul 31.
causes human visceral leishmaniasis and leishmaniosis (CanL) in reservoir host, dogs. As infection progresses to disease in both humans and dogs, there is a shift from controlling type 1 immunity to a regulatory, exhausted T cell phenotype. In endemic areas, the association between tick-borne coinfections (TBCs) and diagnosis and/or clinical severity has been demonstrated. To identify immune factors correlating with disease progression, we prospectively evaluated a cohort of -infected dogs from 2019 to 2022. The cohort was TBC-negative with asymptomatic leishmaniosis at the time of enrollment. We measured TBC serology, anti- antigen T cell immunity, CanL serological response, parasitemia, and disease severity to probe how nascent TBC perturbs the immune state. At the conclusion, TBC+ dogs with CanL experienced greater increases in anti- antibody reactivity and parasite burden compared to dogs that did not have incident TBC during the study. TBC+ dogs were twice as likely to experience moderate (LeishVet stage 2) or severe/terminal disease (LeishVet stage 3/4). Prolonged exposure to TBC was associated with a shift in antigen-induced interferon gamma (IFN-γ)/interleukin-10 (IL-10) and enhanced CD8 T cell proliferation. Frequency of proliferating CD8 T cells significantly correlated with parasitemia and antibody reactivity. TBC exacerbated parasite burden and immune exhaustion. These findings highlight the need for combined vector control efforts as prevention programs for dogs in endemic areas to reduce transmission to humans. Public health education efforts should aim to increase awareness of the connection between TBC and leishmaniosis.
在储存宿主犬中引发人类内脏利什曼病和利什曼iosis（犬利什曼病）。随着感染在人类和犬类中发展为疾病，会从控制1型免疫转变为调节性、耗竭性T细胞表型。在流行地区，蜱传播的共感染（TBCs）与诊断和/或临床严重程度之间的关联已得到证实。为了确定与疾病进展相关的免疫因素，我们前瞻性地评估了一组2019年至2022年感染的犬。该队列在入组时TBC阴性且患有无症状利什曼iosis。我们测量了TBC血清学、抗抗原T细胞免疫、犬利什曼病血清学反应、寄生虫血症和疾病严重程度，以探究新生TBC如何扰乱免疫状态。在研究结束时，与在研究期间未发生TBC的犬相比，患有犬利什曼病的TBC +犬的抗抗体反应性和寄生虫负担增加得更多。TBC +犬发生中度（利什曼兽医阶段2）或重度/终末期疾病（利什曼兽医阶段3/4）的可能性是前者的两倍。长期暴露于TBC与抗原诱导的干扰素γ（IFN-γ）/白细胞介素-10（IL-10）的转变以及增强的CD8 T细胞增殖有关。增殖性CD8 T细胞的频率与寄生虫血症和抗体反应性显著相关。TBC加剧了寄生虫负担和免疫耗竭。这些发现凸显了在流行地区对犬采取联合病媒控制措施作为预防计划以减少向人类传播的必要性。公共卫生教育工作应旨在提高对TBC与利什曼iosis之间联系的认识。
