Ornellas-Garcia Uyla, Freire-Antunes Lucas, Rangel-Ferreira Marcos, de Sousa Carina Heusner Gonçalves, Ribeiro-Almeida Mônica Lucas, Daniel-Ribeiro Cláudio Tadeu, Cuervo Patricia, Ribeiro-Gomes Flávia Lima
Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Centro de Pesquisa, Diagnóstico e Treinamento em Malária, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
PLoS Negl Trop Dis. 2025 Jul 28;19(7):e0013302. doi: 10.1371/journal.pntd.0013302. eCollection 2025 Jul.
Malaria and leishmaniasis are vector-borne diseases responsible for a significant number of deaths worldwide. Despite the co-endemicity of these diseases in regions with tropical and subtropical climates, our understanding of the complex interplay between Plasmodium spp. and Leishmania spp. co-infections on host immune response and resultant disease outcomes remains limited.
METHODOLOGY/PRINCIPAL FINDINGS: This study employs C57BL/6 mice co-infected with Leishmania major and Plasmodium berghei ANKA, well-established models of cutaneous leishmaniasis and experimental cerebral malaria, respectively. Our findings demonstrate that an acute infection with P. berghei ANKA mitigates the progression of ongoing cutaneous leishmaniasis, as evidenced by a reduction in lesion size and parasite burden in the dermis of L. major-infected mice. Co-infection also led to elevated serum levels of TNF compared to the levels observed in mice infected with L. major alone, which may contribute to a more effective control of the Leishmania parasite. Furthermore, co-infected mice exhibited reduced recruitment of activated T cells and inflammatory monocytes to the site of L. major infection. As inflammatory monocytes can be exploited by Leishmania as host cells that support parasite replication, their reduced infiltration may limit parasite growth. This diminished cellular infiltration is likely to contribute to reduced local inflammation, thereby limiting tissue damage and resulting in smaller lesion size.
CONCLUSIONS/SIGNIFICANCE: These findings elucidate the potential cross-regulation of immune responses in co-infections, underscoring the necessity to consider co-infecting pathogens in disease management and therapeutic strategies in endemic areas.
疟疾和利什曼病是由媒介传播的疾病，在全球导致大量死亡。尽管这些疾病在热带和亚热带气候地区共同流行，但我们对疟原虫属和利什曼原虫属共同感染对宿主免疫反应及由此产生的疾病结局之间复杂相互作用的了解仍然有限。
方法/主要发现：本研究使用分别感染硕大利什曼原虫和伯氏疟原虫ANKA的C57BL/6小鼠，它们分别是皮肤利什曼病和实验性脑型疟疾的成熟模型。我们的研究结果表明，急性感染伯氏疟原虫ANKA可减轻正在进行的皮肤利什曼病的进展，这表现为感染硕大利什曼原虫的小鼠真皮中病变大小和寄生虫负荷的降低。与仅感染硕大利什曼原虫的小鼠相比，共同感染还导致血清肿瘤坏死因子水平升高，这可能有助于更有效地控制利什曼原虫寄生虫。此外，共同感染的小鼠在硕大利什曼原虫感染部位的活化T细胞和炎性单核细胞募集减少。由于炎性单核细胞可被利什曼原虫用作支持寄生虫复制的宿主细胞，其浸润减少可能会限制寄生虫生长。这种细胞浸润的减少可能有助于减轻局部炎症，从而限制组织损伤并导致病变尺寸变小。
结论/意义：这些发现阐明了共同感染中免疫反应的潜在交叉调节，强调在流行地区的疾病管理和治疗策略中考虑共同感染病原体的必要性。
