Journal article
Tick-borne coinfections modulate CD8+ T cell response and progressive leishmaniosis
Infection and immunity, Vol.93(9), e00182-25
09/09/2025
DOI: 10.1128/iai.00182-25
PMCID: PMC12418745
PMID: 40741972
Abstract
Leishmania infantum causes human visceral leishmaniasis and leishmaniosis (CanL) in reservoir host, dogs. As infection progresses to disease in both humans and dogs, there is a shift from controlling type 1 immunity to a regulatory, exhausted T cell phenotype. In endemic areas, the association between tick-borne coinfections (TBCs) and Leishmania diagnosis and/or clinical severity has been demonstrated. To identify immune factors correlating with disease progression, we prospectively evaluated a cohort of L. infantum-infected dogs from 2019 to 2022. The cohort was TBC-negative with asymptomatic leishmaniosis at the time of enrollment. We measured TBC serology, anti-Leishmania antigen T cell immunity, CanL serological response, parasitemia, and disease severity to probe how nascent TBC perturbs the immune state. At the conclusion, TBC+ dogs with CanL experienced greater increases in anti-Leishmania antibody reactivity and parasite burden compared to dogs that did not have incident TBC during the study. TBC+ dogs were twice as likely to experience moderate (LeishVet stage 2) or severe/terminal disease (LeishVet stage 3/4). Prolonged exposure to TBC was associated with a shift in Leishmania antigen-induced interferon gamma (IFN-γ)/interleukin-10 (IL-10) and enhanced CD8 T cell proliferation. Frequency of proliferating CD8 T cells significantly correlated with parasitemia and antibody reactivity. TBC exacerbated parasite burden and immune exhaustion. These findings highlight the need for combined vector control efforts as prevention programs for dogs in Leishmania endemic areas to reduce transmission to humans. Public health education efforts should aim to increase awareness of the connection between TBC and leishmaniosis.
Details
- Title: Subtitle
- Tick-borne coinfections modulate CD8+ T cell response and progressive leishmaniosis
- Creators
- Breanna M. Scorza - University of IowaDanielle Pessôa-Pereira - University of IowaFelix Pabon-Rodriguez - Indiana UniversityErin A. Beasley - University of IowaKurayi Mahachi - Eastern Virginia Medical SchoolArin D. Cox - University of PennsylvaniaEric Kontowicz - ,Tyler Baccam - University of IowaGeneva Wilson - Edward Hines, Jr. VA HospitalMax C Waugh - University of IowaShelbe Vollmer - University of IowaAngela Toepp - Eastern Virginia Medical SchoolKavya Raju - ,Ogechukwu C. Chigbo - University of IowaJonah Elliff - University of IowaGreta Becker - University of IowaKaren I. Cyndari - University of IowaSerena Tang - ,Grant Brown - University of Iowa, BiostatisticsChristine A. Petersen - University of Iowa
- Contributors
- Guy H. Palmer (Editor)
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.93(9), e00182-25
- DOI
- 10.1128/iai.00182-25
- PMID
- 40741972
- PMCID
- PMC12418745
- NLM abbreviation
- Infect Immun
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Publisher
- American Society for Microbiology
- Number of pages
- 20
- Grant note
- R01 AI171971 / National Institutes of Health (http://dx.doi.org/10.13039/100000002)
- Language
- English
- Electronic publication date
- 07/31/2025
- Date published
- 09/09/2025
- Academic Unit
- Epidemiology; Emergency Medicine; Biostatistics; Obstetrics and Gynecology
- Record Identifier
- 9984927089302771
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