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Am J Trop Med Hyg. 2019 Sep;101(3):585-589. doi: 10.4269/ajtmh.19-0160.

Elevated Activation of Neutrophil Toll-Like Receptors in Patients with Acute Severe Leptospirosis: An Observational Study.

Author information

1
Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Brazilian Ministry of Health, Salvador, Brazil.
2
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut.
3
Section of Rheumatology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
4
Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
5
Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
6
Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.

Abstract

Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. Although neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of toll-like receptors 2 and 4 (TLR2 and TLR4, respectively) on peripheral neutrophils than healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation), regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.

PMID:
31333152
PMCID:
PMC6726964
[Available on 2020-09-01]
DOI:
10.4269/ajtmh.19-0160

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