Pulmonary Disease in Hamsters Infected with Leptospira interrogans: Histopathologic Findings and Cytokine mRNA Expressions

Abstract

Abstract. Our aim was to evaluate the pulmonary changes induced by Leptospira interrogans infection in hamsters, and the gene expression of endogenous mediators in lung fragments during 28 days of observation. The animals were euthanized on days 4, 7, 14, 21, and 28 post-inoculation. Histopathologic lung analysis showed hemorrhage, pneumonia, alveolar congestion, and infiltrated cellular areas, with increasing severity until day 21 post-inoculation. Tumor necrosis factor (TNF)-a mRNA expression enhanced in first days with peak on day 4 and slightly decreased in the final phase. The interleukin (IL)-10 remained relatively constant throughout the period, with the exceptions of days 4 and 14. The endothelial nitric-oxide synthesis (eNOS) showed an increased expression on day 4, followed by an augment on days 7 and 14, and remaining constant up to day 28 post-infection. Our results demonstrate that inoculation of L. interrogans sorovar Icterohaemorrhagiae induced pulmonary lesions, including pulmonary hemorrhage, supporting that the lung is a target organ.

Gene Expression Profiles of Immune Mediators and Histopathological Findings in Animal Models of Leptospirosis: Comparison between Susceptible Hamsters and Resistant Mice

“…For each organ, formalinfixed paraffin-embedded tissue blocks were subjected to hematoxylin-erythrosinsafran (HES) staining for tissue sections of 2 to 3.5 m. Leptospires were visualized after silver impregnation following the Warthin-Starry (WS) protocol modified with pyrocatechol as described by Wuscher and Huerre (60). Lesions in target organs were graded (see Table 2) according to previously reported criteria (26,33,35,53,64).…”

“…The histopathological analysis of the lungs of hamsters infected with L. interrogans serovar Icterohaemorrhagiae showed hemorrhage, alveolar congestion, and infiltrated cellular areas associated with both TNF-␣ and IL-10 overexpression (26). In the kidneys of hamsters infected with L. interrogans serovar Pyrogenes, IP-10/CXCL10, IL-10, transforming growth factor ␤ (TGF-␤), and TNF-␣ were also overexpressed, suggesting a role of T cell recruitment in the immune response and the pathology of renal leptospirosis (21).…”

Genotipificación y evaluación de la dinámica de infección de un aislamiento colombiano de Leptospira santarosai en el modelo experimental hámster

“…(20,(39)(40)(41)(42)(43)(44)(45). Entre estos hallazgos resaltamos los estudios en hámster y tití común (Callithrix jacchus) con especies patógenas de diferente origen y bajo diferentes protocolos de infección.…”

“…En estas infecciones se encontraron lesiones pulmonares y de riñón que variaban de leves a graves, semejantes a las encontradas en el presente estudio en el modelo de hámster infectado con L. santarosai (40)(41)(42)(43). Del mismo modo, Arean, et al, (39) en las necropsias de casos fatales en humanos, describieron diferentes grados de compromiso pulmonar, particularmente los caracterizados por áreas de hemorragia, edema y congestión alveolar, lo que se asemeja a lo encontrado en este estudio en el modelo de hámster-L. santarosai. La capacidad invasiva de L. santarosai en los órganos blanco (pulmón, riñón) del hámster se pudo demostrar mediante la coloración de WarthinStarry, el aislamiento en cultivo a partir del triturado de estos órganos y el resultado positivo en la PCR lipL32.…”

Importância do componente C5 do sistema complemento para o controle de leptospirose in vivo em modelos murinos.

“…Camundongos normalmente resistentes à Leptospira podem se tornar susceptíveis se tratados com ciclofosfamida, uma substância imunossupressora que inibe a atividade de linfócitos B e impede a produção de anticorpos, afetando consequentemente a imunidade humoral (Adler, Faine, 1976; . Contudo, mesmo linhagens de camundongos naturalmente susceptíveis a leptospiras podem não apresentar lesões pulmonares quando infectadas com doses consideradas letais para hamsters, sendo necessário aplicar inóculos com grandes quantidades de leptospiras para induzir danos nesse órgão (Marinho et al, 2009;Nally et al, 2005;Viriyakosol et al, 2006). Entre os danos observados no tecido hepático, há desestruturação do padrão de organização das células, pontos de necrose, infiltrados celulares e aumento do número de células de Küppfer.…”