During visceral leishmaniasis (VL), T helper 1 (Th1)-based inflammation is induced to control intracellular parasites. Inflammation-based pathology has been shown to be dampened by interleukin 10 and eventual Programmed Death1 (PD1)-mediated T cell exhaustion. Cell type(s) responsible for the initiation of T cell-produced IL-10 during VL are unknown. CD19+, CD5−, CD1d−, IgDhi regulatory B cells from healthy controls produced IL-10 in absence of infection or stimulation in contrast to IgDlo/neg B cells. IgDhi B cells may have a de novo vs. induced regulatory program. IgDhi B cells increased three-fold in population size as VL progressed. B cells from VL dogs were necessary and sufficient to suppress T helper 1 (Th1) cell effector function. IgDhi B cells induced T cell and IgDlo B cell IL-10 production. Blockage of B cell-specific PD-L1 restored Th1 responses. IgDhi regulatory B cells represent a novel regulatory B cell which may precipitate T cell exhaustion during VL.
BackgroundVisceral leishmaniasis (VL) is a vector borne zoonotic disease endemic in humans and dogs in Brazil. Due to the increased risk of human infection secondary to the presence of infected dogs, public health measures in Brazil mandate testing and culling of infected dogs. Despite this important relationship between human and canine infection, little is known about what makes the dog reservoir progress to clinical illness, significantly tied to infectiousness to sand flies. Dogs in endemic areas of Brazil are exposed to many tick-borne pathogens, which are likely to alter the immune environment and thus control of L. infantum.ResultsA cross-sectional study of 223 dogs from an area of Natal, in the Rio Grande do Norte, Brazil, were studied to determine the association between comorbid tick-borne disease and Leishmania infection in this endemic area. The risk of Leishmania seropositivity was 1.68× greater in dogs with tick-borne disease seropositivity compared to those without (Adjusted RR: 1.68, 95% CI: 1.09–2.61, P = 0.019). A longitudinal study of 214 hunting dogs in the USA was conducted to determine the causal relationship between infection with tick-borne diseases and progression of VL. Hunting dogs were evaluated three times across a full tick season to detect incident infection with tick-borne diseases. A logistic regression model with generalized estimating equations to estimate the parameters was used to determine how exposure to tick-borne disease altered VL progression over these three time points when controlling for other variables. Dogs infected with three or more tick-borne diseases were 11× more likely to be associated with progression to clinical VL than dogs with no tick-borne disease (Adjusted RR: 11.64, 95% CI: 1.22–110.99, P = 0.03). Dogs with exposure to both Leishmania spp. and tick-borne diseases were five times more likely to die during the study period (RR: 4.85, 95% CI: 1.65–14.24, P = 0.0051).ConclusionsComorbid tick-borne diseases dramatically increased the likelihood that a dog had clinical L. infantum infection, making them more likely to transmit infection to sand flies and people. As an important consequence, reduction of tick-borne disease exposure through topical or oral insecticides may be an important way to reduce progression and transmissibility of Leishmania infection from the canine reservoir to people.Electronic supplementary materialThe online version of this article (10.1186/s13071-019-3312-3) contains supplementary material, which is available to authorized users.
Canine leishmaniosis (CanL) is caused by Leishmania infantum, an obligate intracellular protozoan parasite, endemic in U.S. hunting dog populations. CanL has been found in dogs in 28 states and two Canadian provinces. Previous studies by our group, (Boggiatto, 2011), demonstrated that vertical transmission of Leishmania was the predominant means of transmission within U.S. dogs. Very little is known regarding how this alternative means of transmission, alters the long-term immunity and clinical presentation of leishmaniosis in dogs born to a positive bitch. This study follows the immunological progression of CanL in three pups after birth to an infected bitch. During the course of the study, these dogs were tested every six months over the course of six years. Both immunologic (IFN-γ, T cell proliferation, antibody production) and parasitological parameters (qPCR) of vertically-infected dogs were measured. Within the six years after birth to an L. infantum-infected, oligosymptomatic bitch, all dogs had at least one L. infantum PCR-positive test. Interestingly, despite living in the same location for their entire lives and being full siblings, these pups demonstrate three different disease progression patterns of L. infantum infection. One dog progressed to oligosymptomatic disease, maintaining a positive titer and had intermittent positive PCR results. One asymptomatic dog had positive serological titers and demonstrated a robust CD4+ immune response to infection. The third dog had a negligible response to L. infantum antigen and was healthy. This work demonstrates the biologic variability associated with vertically-transmitted infection similar to the variety of presentations observed during vector-borne leishmaniosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.