Abstract
Recent estimates on global morbidity and mortality caused by Leptospirosis point to one million cases and almost 60,000 deaths a year worldwide, especially in resource poor countries. We analyzed how a commensal probiotic immunomodulator, Lactobacillus plantarum, affects Leptospira interrogans pathogenesis in a murine model of sub-lethal leptospirosis. We found that repeated oral pre-treatment of mice with live L. plantarum restored body weight to normal levels in mice infected with L. interrogans. Pre-treatment did not prevent L. interrogans access to the kidney but it affected the inflammatory response and it reduced histopathological signs of disease. Analysis of the immune cell profiles in lymphoid tissues of mice pre-treated with L. plantarum showed increased numbers of B cells as well as naïve and memory CD4+ helper T cell populations in uninfected mice that shifted towards increased numbers of effector CD4+ helper T in infected mice. CD8+ cytotoxic T cell profiles in pre-treated uninfected and infected mice mirrored the switch observed for CD4+ except that CD8+ memory T cells were not affected. In addition, pre-treatment led to increased populations of monocytes in lymphoid tissues of uninfected mice and to increased populations of macrophages in the same tissues of infected mice. Immunohistochemistry of kidney sections of pre-treated infected mice showed an enrichment of neutrophils and macrophages and a reduction of total leucocytes and T cells. Our results suggest that complex myeloid and T cell responses orchestrate the deployment of monocytes and other cells from lymphoid tissue and the recruitment of neutrophils and macrophages to the kidney, and that, the presence of these cells in the target organ may be associated with reductions in pathogenesis observed in infected mice treated with L. plantarum.
Highlights
A recent review on global morbidity and mortality caused by Leptospirosis estimates about 1.03 million cases and 58,900 deaths a year worldwide [1], mostly in resource-poor countries [2][3]
In this study we describe how repeated oral treatment of mice with a commonly used probiotic, Lactobacillus plantarum, did not completely prevent colonization of the kidney by Leptospira interrogans but it did reduce signs and symptoms of leptospirosis
Our results suggest that pre-treatment with L. plantarum modulates systemic immune responses in a beneficial way in a mammalian host later exposed to L. interrogans infection
Summary
A recent review on global morbidity and mortality caused by Leptospirosis estimates about 1.03 million cases and 58,900 deaths a year worldwide [1], mostly in resource-poor countries [2][3]. Human leptospirosis is an acute febrile illness with a broad clinical spectrum ranging from mild influenza-like symptoms to severe disease forms characterized by bleeding, jaundice, renal failure, pulmonary hemorrhage and death [2, 3]. Most leptospirosis patients recover without treatment [3, 4], diagnosis of the disease is hindered by the complexity and insensitivity of serology by the microagglutination test (MAT) in acute infection [5]. Vaccines to prevent human disease exist in some countries and are based in killed whole cell Leptospira [3]. These vaccines provide only short-time protection, are serovar specific and mostly target leptospiral LPS [2]
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