Journal article
Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi
Pathogens (Basel), Vol.12(9), p.1128
09/04/2023
DOI: 10.3390/pathogens12091128
PMCID: PMC10537792
PMID: 37764937
Abstract
Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFN gamma. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs.
Details
- Title: Subtitle
- Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi
- Creators
- Danielle Pessoa-Pereira - University of IowaBreanna M. Scorza - University of IowaKaren I. Cyndari - University of Iowa Hospitals and ClinicsErin A. Beasley - University of IowaChristine A. Petersen - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Pathogens (Basel), Vol.12(9), p.1128
- DOI
- 10.3390/pathogens12091128
- PMID
- 37764937
- PMCID
- PMC10537792
- NLM abbreviation
- Pathogens
- ISSN
- 2076-0817
- eISSN
- 2076-0817
- Publisher
- Mdpi
- Number of pages
- 20
- Grant note
- Carver College of Medicine Iowa City Veteran's Administration Medical Center We thank the animal caretakers for their time and participation in this study. We acknowledge Mary Wilson for providing access to critical equipment. The data presented herein were obtained at the Flow Cytometry Facility, which is a Carver College of Medic
- Language
- English
- Date published
- 09/04/2023
- Academic Unit
- Epidemiology; Emergency Medicine; Obstetrics and Gynecology
- Record Identifier
- 9984696654102771
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