Role of inducible nitric oxide synthase in the pathogenesis of experimental leptospirosis

Pretre, Gabriela; Olivera, Noelia; Cédola, Maia Tatiana; Haase, Santiago; Alberdi, Lucrecia; Brihuega, Bibiana; Gómez, Ricardo Martín

doi:10.1016/j.micpath.2011.03.011

Cited by 23 publications

(30 citation statements)

References 41 publications

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“…However, by using several transgenic mice, a very recent study elegantly showed that TLR and NLR receptors as well as T lymphocytes are not required to generate Leptospira -induced renal fibrosis. Instead, the iNOS enzyme, known to play a role in Leptospira -induced interstitial nephritis [43], [44], was associated with the induction of renal fibrosis [45]. Given that in Daf1 −/− mice the increase in inflammation and fibrosis was not correlated with an increase in the bacterial burden present in the kidneys of chronically infected mice, we conclude that the major factors driving fibrosis in this model rely on the presence of leptospires during the early stages, and on the host response in the chronic phase without excluding a role for enhanced complement-mediated injury and/or reduced turnover of extracellular matrix components.…”

Section: Discussionmentioning

confidence: 99%

Decay-Accelerating Factor 1 Deficiency Exacerbates Leptospiral-Induced Murine Chronic Nephritis and Renal Fibrosis

et al. 2014

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Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1−/− mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1−/− mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1−/− mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1−/− mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

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Section: Discussionmentioning

confidence: 99%

Decay-Accelerating Factor 1 Deficiency Exacerbates Leptospiral-Induced Murine Chronic Nephritis and Renal Fibrosis

et al. 2014

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“…(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.…”

Section: Discussionunclassified

“…Este hallazgo sugiere que la modulación de la respuesta inmunitaria está determinando la presentación de signos clínicos y, por consiguiente, la evolución final de la enfermedad (20,31,33).…”

Section: Discussionunclassified

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

et al. 2014

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“…Production of iNOS is important for host survival (Prêtre et al 2011), but two studies have suggested that iNOS activity may contribute to damage observed during Leptospira-induced pulmonary hemorrhage Yang and Hsu 2005).…”

Section: Immune Pathologymentioning

confidence: 99%

Host Response to Leptospira Infection

Zuerner

2014

Current Topics in Microbiology and Immunology

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Pathogenic Leptospira has the capacity to infect a broad range of mammalian hosts. Leptospirosis may appear as an acute, potentially fatal infection in accidental hosts, or progress into a chronic, largely asymptomatic infection in natural maintenance hosts. The course that Leptospira infection follows is dependent upon poorly understood factors, but is heavily influenced by both the host species and bacterial serovar involved in infection. Recognition of pathogen-associated molecular patterns (PAMPs) by a variety of host pattern recognition receptors (PRRs) activates the host immune system. The outcome of this response may result in bacterial clearance, limited bacterial colonization of a few target organs, principally the kidney, or induction of sepsis as the host succumbs to infection and dies. This chapter describes current knowledge of how the host recognizes Leptospira and responds to infection using innate and acquired immune responses. Aspects of immune-mediated pathology and pathogen strategies to evade the host immune response are also addressed.

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Role of inducible nitric oxide synthase in the pathogenesis of experimental leptospirosis

Cited by 23 publications

References 41 publications

Decay-Accelerating Factor 1 Deficiency Exacerbates Leptospiral-Induced Murine Chronic Nephritis and Renal Fibrosis

Decay-Accelerating Factor 1 Deficiency Exacerbates Leptospiral-Induced Murine Chronic Nephritis and Renal Fibrosis

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

Host Response to Leptospira Infection

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