Santos-Oliveira Joanna Reis, Silva-Freitas Maria Luciana, Cappato Marcelle da Senhora, Marques-Paulo Elaine, Paiva Milla Bezerra, Soares Sandra Regina, de Oliveira Dayane Alvarinho, Lopes-Torres Eduardo José, Pelajo-Machado Marcelo, Pinto Eduardo Fonseca, Lindoso Jose Angelo L, Goto Hiro, Da-Cruz Alda M
Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório Interdisciplinar de Pesquisas Médicas, Rio de Janeiro, RJ, Brasil.
Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Núcleo de Ciências Biomédicas Aplicadas, Rio de Janeiro, RJ, Brasil.
Mem Inst Oswaldo Cruz. 2025 Sep 8;120:e240266. doi: 10.1590/0074-02760240266. eCollection 2025.
Parasite antigens and plasma lipopolysaccharide (LPS) levels from luminal origin in visceral leishmaniasis (VL) patients are correlated with cellular activation and low CD4+T cell counts.
Our aim was to verify whether Leishmania infantum infection damages the intestinal barrier and whether combination antimonial/antibiotic contributes to the reduction of LPS levels and immune activation.
Golden hamsters were grouped in: G1-uninfected; G2-infected with L. infantum; and G3/G4 and G5-infected, treated with antimonial, antibiotic or both drugs, respectively. The treatment initiated 45 days post infection (dpi), daily by 10 days.
G2, G3, and G4 animals showed a significant increase in spleen weight compared to G1. An elevated parasite load was observed in G2, unlike the G3, G4, and especially, G5, whose decrease was significant at 120 dpi. Intestinal mucosal alterations and elevated LPS levels were observed in G2 group. However, G3, G4 and G5 animals showed lower LPS levels than G2. Moreover, G4 and G5 presented higher CD4+T-cell percentages and lower activation levels than G2 and G3, either at 60 or 101-120 dpi.
Our results showed evidence of bacterial translocation in experimental VL and that the concomitant use of antimonial and antibiotic may reduce LPS levels, along with an improvement of the immunosuppression and reduction of lymphocyte activation.
内脏利什曼病（VL）患者体内源自管腔的寄生虫抗原和血浆脂多糖（LPS）水平与细胞活化及低CD4 + T细胞计数相关。
我们的目的是验证婴儿利什曼原虫感染是否会损害肠道屏障，以及锑剂/抗生素联合使用是否有助于降低LPS水平和免疫激活。
将金黄仓鼠分为：G1组 - 未感染；G2组 - 感染婴儿利什曼原虫；G3/G4组和G5组 - 感染后分别用锑剂、抗生素或两种药物治疗。治疗在感染后45天（dpi）开始，每天进行，持续10天。
与G1组相比，G2、G3和G4组动物的脾脏重量显著增加。G2组观察到寄生虫负荷升高，与G3、G4组不同，尤其是G5组，其在120 dpi时寄生虫负荷显著下降。G2组观察到肠道黏膜改变和LPS水平升高。然而，G3、G4和G5组动物的LPS水平低于G2组。此外，在60 dpi或101 - 120 dpi时，G4和G5组的CD4 + T细胞百分比高于G2和G3组，活化水平低于G2和G3组。
我们的结果显示实验性VL存在细菌移位的证据，并且锑剂和抗生素联合使用可能会降低LPS水平，同时改善免疫抑制并减少淋巴细胞活化。
