Gene expression is associated with virulence in murine macrophages infected with Leptospira spp
Erivelto Corrêa de Araújo, Leandro Encarnação GarciaiD, Matheus Janeck AraújoiD, Itamar Souza de Oliveira-JúnioriD, Daniel R. ArnoldiD, Flávia Lombardi LopesiD, Márcia MarinhoiD
Abstract
Leptospira genus contains species that affect human health with varying degrees of pathogenicity. In this context, we aimed to evaluate the differences in modulation of host gene expression by strains of Leptospira with varied virulence degrees. Our data showed a high number of differentilly expressed transcripts in murine macrophages following 6h of infection with both virulent and culture-attenuated L. interrogans and to a lesser degree, with the saprophyte strain L. biflexa. That suggests that certain genes are modulated by Leptospira infection independent of their degree of virulence, whether others are virulence and species associated. Pathway analysis indicated that Apoptosis, ATM Signaling and Cell Cycle: G2/M DNA Damage Checkpoint Regulation were exclusively regulated following infection with the virulent strain. Results demonstrated that species and virulence play a role during host response to Leptosppira spp in murine macrophages.\n\nAuthor summaryLeptospirosis is an infectious disease that is transmitted from animals to humans. It is a re-emerging neglected zoonosis that is found in a range of environments worldwide, most notably tropical regions prone to flooding. This bacteria is found in soil and water and are eliminated in the urine by rats, their natural host reservoir. Through skin contacts with the bacteria people or animals can get infected however the infection process is still poorly understood, such as the fact that different strains can cause different severity of illness. In this study, we aimed to evaluate the differences in modulation of host gene expression by strains of Leptospira varying in virulence. After transcriptomic analysis, the results showed a high number of differentially expressed genes after 6h of infection by virulent and attenuated L. interrogans, and to a lesser extent with L. biflexa saprophytic lineage. This suggests that RNAs are modulated after infection by Leptospira in macrophages, in a species and virulence related manner. It is hoped that the data produced will contribute to further our understanding on the pathogenesis of leptospirosis.
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