Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi.
Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi.
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DOI：
10.3390/pathogens12091128
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发表时间：
2023-09-04
期刊：
影响因子：
--
通讯作者：
Petersen CA
中科院分区：
文献类型：
--
作者：
Pessôa-Pereira D;Scorza BM;Cyndari KI;Beasley EA;Petersen CA
犬利什曼病（CanL）是由婴儿利什曼原虫（Leishmania infantum）引起的人畜共患疾病。患有CanL的狗通常会同时感染蜱传细菌病原体，包括美国的伯氏疏螺旋体。这些合并感染与加速疾病进展和死亡率有因果关系。然而，混合感染如何影响抗L.婴儿未知。我们假设B. burgdorferi共感染影响宿主巨噬细胞效应子功能，促使L.婴儿细胞内存活率。体外实验表明，暴露于B。伯氏螺旋体显著提高了L.婴儿寄生虫负荷和DH 82犬巨噬细胞中的促炎反应。与未感染和L.婴儿感染的细胞来自L.具有螺旋体和/或总利什曼原虫抗原的婴儿血清阴性和血清阳性亚临床犬促进IFNγ的有限诱导。共暴露显著诱导了促炎细胞因子和趋化因子的表达，这些因子与来自L.婴儿血清反应阳性的狗过度的促炎反应先前已被证明会导致CanL病理学。这项工作支持有效的蜱预防和合并感染的风险管理作为预防和控制L。犬的婴儿期进展。
Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFNγ. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs.
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DOI：
10.3390/ani11113206
发表时间：
2021-11-10
期刊：
Animals : an open access journal from MDPI
影响因子：
--
作者：
Beasley EA;Pessôa-Pereira D;Scorza BM;Petersen CA
通讯作者：
Petersen CA
DOI：
10.4049/jimmunol.1301810
发表时间：
2013-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Esch KJ;Juelsgaard R;Martinez PA;Jones DE;Petersen CA
通讯作者：
Petersen CA
影响因子：
4.4
作者：
Ball, Writoban Basu;Kar, Susanta;Das, Pijush K.
通讯作者：
Das, Pijush K.
影响因子：
4.4
作者：
Bitsaktsis, C;Huntington, J;Winslow, G
通讯作者：
Winslow, G
影响因子：
3
作者：
Benjamin SJ;Hawley KL;Vera-Licona P;La Vake CJ;Cervantes JL;Ruan Y;Radolf JD;Salazar JC
通讯作者：
Salazar JC