Exposure to live saprophyticLeptospirabefore challenge with a pathogenic serovar prevents severe leptospirosis and promotes kidney homeostasis

Abstract

ABSTRACTPrevious studies demonstrated thatLeptospira biflexa, a saprophytic species, triggers innate immune responses in the host during early infection. This raised the question of whether these responses could suppress a subsequent challenge with pathogenicLeptospira. We inoculated C3H/HeJ mice with a single or a double dose ofL. biflexabefore challenge with a pathogenic serovar,L. interrogansserovar Copenhageni FioCruz (LIC). Pre-challenge exposure toL. biflexadid not prevent LIC dissemination and colonization of the kidney. However, it rescued weight loss and mouse survival thereby mitigating disease severity. Unexpectedly, there was correlation between rescue of overall health (weight gain, higher survival, lower kidney fibrosis marker ColA1) and higher shedding of LIC in urine. This stood in contrast to theL. biflexaunexposed LIC challenged control. Immune responses were dominated by increased frequency of effector T helper (CD4+) cells in spleen, as well as significant increases in serologic IgG2a. Our findings suggest that exposure to live saprophyticLeptospiraprimes the host to develop Th1 biased immune responses that prevent severe disease induced by a subsequent challenge with a pathogenic species. Thus, mice exposed to live saprophyticLeptospirabefore facing a pathogenic serovar may withstand infection with far better outcomes. Furthermore, a status of homeostasis may have been reached after kidney colonization that helps LIC complete its enzootic cycle.SignificancePrevious evidence of host innate immunity induced by live saprophyticLeptospirain mice led us to posit that these responses might mitigate leptospirosis severity upon a subsequent challenge with a pathogenic serovar. In this study, we validated our hypothesis. This is important for development of novel strategies to control leptospirosis and for understanding the epidemiologic risk factors of this and other infectious diseases transmitted by direct contact between pathogen and host. Unexpectedly, these studies also show that there is a correlation between kidney health afterL. interrogansinfection (less fibrosis marker ColA1) and higher shedding of this spirochete in urine. This suggests that a status of homeostasis may be reached after kidney colonization byL. interrogansthat helps the spirochete fulfill its enzootic cycle.