Leptospirosis Pathophysiology: Into the Storm of Cytokines
Leptospirosis is a neglected tropical zoonosis caused by pathogenic spirochetes of the genus Leptospira. Infected reservoir animals, typically mice and rats, are asymptomatic, carry the pathogen in their renal tubules, and shed pathogenic spirochetes in their urine, contaminating the environment. Hu...
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doaj-d4173e0446c349b798fb08b78dd7bda32020-11-25T02:28:46ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-06-01810.3389/fcimb.2018.00204274770Leptospirosis Pathophysiology: Into the Storm of CytokinesJulie Cagliero0Sharon Y. A. M. Villanueva1Mariko Matsui2Group Immunity and Inflammation, Institut Pasteur International Network, Institut Pasteur in New Caledonia, Nouméa, New CaledoniaDepartment of Medical Microbiology, College of Public Health, University of the Philippines, Manila, PhilippinesGroup Immunity and Inflammation, Institut Pasteur International Network, Institut Pasteur in New Caledonia, Nouméa, New CaledoniaLeptospirosis is a neglected tropical zoonosis caused by pathogenic spirochetes of the genus Leptospira. Infected reservoir animals, typically mice and rats, are asymptomatic, carry the pathogen in their renal tubules, and shed pathogenic spirochetes in their urine, contaminating the environment. Humans are accidental hosts of pathogenic Leptospira. Most human infections are mild or asymptomatic. However, 10% of human leptospirosis cases develop into severe forms, including high leptospiremia, multi-organ injuries, and a dramatically increased mortality rate, which can relate to a sepsis-like phenotype. During infection, the triggering of the inflammatory response, especially through the production of cytokines, is essential for the early elimination of pathogens. However, uncontrolled cytokine production can result in a cytokine storm process, followed by a state of immunoparalysis, which can lead to sepsis and associated organ failures. In this review, the involvement of cytokine storm and subsequent immunoparalysis in the development of severe leptospirosis in susceptible hosts will be discussed. The potential contribution of major pro-inflammatory cytokines in the development of tissue lesions and systemic inflammatory response, as well as the role of anti-inflammatory cytokines in contributing to the onset of a deleterious immunosuppressive cascade will also be examined. Data from studies comparing susceptible and resistant mouse models will be included. Lastly, a concise discussion on the use of cytokines for therapeutic purposes or as biomarkers of leptospirosis severity will be provided.https://www.frontiersin.org/article/10.3389/fcimb.2018.00204/fullLeptospiraleptospirosisinflammatory responsecytokine stormimmunoparalysissusceptible/resistant hosts |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julie Cagliero Sharon Y. A. M. Villanueva Mariko Matsui |
spellingShingle |
Julie Cagliero Sharon Y. A. M. Villanueva Mariko Matsui Leptospirosis Pathophysiology: Into the Storm of Cytokines Frontiers in Cellular and Infection Microbiology Leptospira leptospirosis inflammatory response cytokine storm immunoparalysis susceptible/resistant hosts |
author_facet |
Julie Cagliero Sharon Y. A. M. Villanueva Mariko Matsui |
author_sort |
Julie Cagliero |
title |
Leptospirosis Pathophysiology: Into the Storm of Cytokines |
title_short |
Leptospirosis Pathophysiology: Into the Storm of Cytokines |
title_full |
Leptospirosis Pathophysiology: Into the Storm of Cytokines |
title_fullStr |
Leptospirosis Pathophysiology: Into the Storm of Cytokines |
title_full_unstemmed |
Leptospirosis Pathophysiology: Into the Storm of Cytokines |
title_sort |
leptospirosis pathophysiology: into the storm of cytokines |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2018-06-01 |
description |
Leptospirosis is a neglected tropical zoonosis caused by pathogenic spirochetes of the genus Leptospira. Infected reservoir animals, typically mice and rats, are asymptomatic, carry the pathogen in their renal tubules, and shed pathogenic spirochetes in their urine, contaminating the environment. Humans are accidental hosts of pathogenic Leptospira. Most human infections are mild or asymptomatic. However, 10% of human leptospirosis cases develop into severe forms, including high leptospiremia, multi-organ injuries, and a dramatically increased mortality rate, which can relate to a sepsis-like phenotype. During infection, the triggering of the inflammatory response, especially through the production of cytokines, is essential for the early elimination of pathogens. However, uncontrolled cytokine production can result in a cytokine storm process, followed by a state of immunoparalysis, which can lead to sepsis and associated organ failures. In this review, the involvement of cytokine storm and subsequent immunoparalysis in the development of severe leptospirosis in susceptible hosts will be discussed. The potential contribution of major pro-inflammatory cytokines in the development of tissue lesions and systemic inflammatory response, as well as the role of anti-inflammatory cytokines in contributing to the onset of a deleterious immunosuppressive cascade will also be examined. Data from studies comparing susceptible and resistant mouse models will be included. Lastly, a concise discussion on the use of cytokines for therapeutic purposes or as biomarkers of leptospirosis severity will be provided. |
topic |
Leptospira leptospirosis inflammatory response cytokine storm immunoparalysis susceptible/resistant hosts |
url |
https://www.frontiersin.org/article/10.3389/fcimb.2018.00204/full |
work_keys_str_mv |
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