Abstract
Cattle are the reservoir hosts of Leptospira borgpetersenii serovar Hardjo, and can also be reservoir hosts of other Leptospira species such as L. kirschneri, and Leptospira interrogans. As a reservoir host, cattle shed Leptospira, infecting other animals, including humans. Previous studies with human and murine neutrophils have shown activation of neutrophil extracellular trap or NET formation, and upregulation of inflammatory mediators by neutrophils in the presence of Leptospira. Humans, companion animals and most widely studied models of Leptospirosis are of acute infection, hallmarked by systemic inflammatory response, neutrophilia, and septicemia. In contrast, cattle exhibit chronic infection with few outward clinical signs aside from reproductive failure. Taking into consideration that there is host species variation in innate immunity, especially in pathogen recognition and response, the interaction of bovine peripheral blood polymorphonuclear cells (PMNs) and several Leptospira strains was evaluated. Studies including bovine-adapted strains, human pathogen strains, a saprophyte and inactivated organisms. Incubation of PMNs with Leptospira did induce slight activation of neutrophil NETs, greater than unstimulated cells but less than the quantity from E. coli P4 stimulated PMNs. Very low but significant from non-stimulated, levels of reactive oxygen peroxides were produced in the presence of all Leptospira strains and E. coli P4. Similarly, significant levels of reactive nitrogen intermediaries (NO2) was produced from PMNs when incubated with the Leptospira strains and greater quantities in the presence of E. coli P4. PMNs incubated with Leptospira induced RNA transcripts of IL-1β, MIP-1α, and TNF-α, with greater amounts induced by live organisms when compared to heat-inactivated leptospires. Transcript for inflammatory cytokine IL-8 was also induced, at similar levels regardless of Leptospira strain or viability. However, incubation of Leptospira strains with bovine PMNs did not affect Leptospira viability as measured by limiting dilution culture. This is in contrast to previously reported results of innate inflammatory activation by Leptospira in human and other animal models, or the activation and interaction of bovine PMNs with Escherichia coli and other bacterial pathogens. While it could be hypothesized that variations in innate receptor recognition, specifically variance in toll-like receptor 2, could underlie the observed reduction of activation in bovine PMNs, additional studies would be needed to explore this possibility. Reduction in neutrophil responses may help to establish nearly asymptomatic chronic Leptospira infection of cattle. This study emphasizes the importance of studying host-pathogen relationships in the appropriate species as extrapolation from other animal models may be incorrect and confounded by differences in the host responses.
Highlights
Leptospirosis is a disease caused by pathogenic spirochetes in the genus Leptospira, incorporating numerous species and over 200 serovars
While there appeared to be an increase in the numbers of cells stained with the permeable dye when polymorphonuclear cells (PMNs) were incubated with Leptospira (Figures 1C–E), E. coli P4 (Figure 1B) or Phorbol 12-myristate 13acetate (PMA) (Figure 1F) over the unstimulated PMNs per field of view (Figure 1A), these results could not be quantitated due to uneven distribution of cells on the slide, variability across individual slides and variability from experimental day to day
Incubation with Leptospira strains induced approximately a two-fold increase in supernatant DNA concentration compared to non-stimulated PMNs resulting in strain 203.27.3 ng/ml, JB197 26.6 ng/ml, RM211 26.8 ng/ml, Fiocruz 28.3 ng/ml, Patoc 24.8 ng/ml, heatkilled JB197 24.3 ng/ml which were all statistically different from no stimulant, E. coli P4 and PMA (p < 0.0001) but not among the Leptospira strains (p < 0.05)
Summary
Leptospirosis is a disease caused by pathogenic spirochetes in the genus Leptospira, incorporating numerous species and over 200 serovars. Chronically infected, reservoir hosts are generally asymptomatic with intermittent shedding of bacteria in urine. Cattle are most commonly infected with Leptospira borgpetersenii serovar Hardjo. Leptospirosis infection is the leading cause of reproductive failure in cattle, and can result in weak/stillborn calves, reduced growth rates, and reduced milk production, all contributing to considerable economic loss to the cattle producer. Some cattle develop a chronic infection/shedding state and serve as a reservoir of infection for cattle and other incidental hosts including humans. Serovar Hardjo infection in incidental hosts, like humans or dogs, can result in acute disease (Blackmore and Schollum, 1982; Ryan et al, 1982; Zuerner et al, 2012)
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