RGD Reference Report - Lymphocytic Choriomeningitis Virus Expands a Population of NKG2D+CD8+ T Cells That Exacerbates Disease in Mice Coinfected with Leishmania major. - Rat Genome Database

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Lymphocytic Choriomeningitis Virus Expands a Population of NKG2D+CD8+ T Cells That Exacerbates Disease in Mice Coinfected with Leishmania major.

Authors: Crosby, Erika J  Clark, Megan  Novais, Fernanda O  Wherry, E John  Scott, Phillip 
Citation: Crosby EJ, etal., J Immunol. 2015 Oct 1;195(7):3301-10. doi: 10.4049/jimmunol.1500855. Epub 2015 Aug 19.
RGD ID: 39128165
Pubmed: PMID:26290604   (View Abstract at PubMed)
PMCID: PMC4575880   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.1500855   (Journal Full-text)

Leishmaniasis is a significant neglected tropical disease that is associated with a wide range of clinical presentations and a lifelong persistent infection. Because of the chronic nature of the disease, there is a high risk for coinfection occurring in patients, and how coinfections influence the outcome of leishmaniasis is poorly understood. To address this issue, we infected mice with Leishmania major and 2 wk later with lymphocytic choriomeningitis virus (LCMV) and then monitored the course of infection. Leishmania parasites are controlled by production of IFN-γ, which leads to macrophage-mediated parasite killing. Thus, one might predict that coinfection with LCMV, which induces a strong systemic type 1 response, would accelerate disease resolution. However, we found that infection with LCMV led to significantly enhanced disease in L. major-infected animals. This increased disease correlated with an infiltration into the leishmanial lesions of NKG2D(+) CD8(+) T cells producing granzyme B, but surprisingly little IFN-γ. We found that depletion of CD8 T cells after viral clearance, as well as blockade of NKG2D, reversed the increased pathology seen in coinfected mice. Thus, this work highlights the impact a secondary infection can have on leishmaniasis and demonstrates that even pathogens known to promote a type 1 response may exacerbate leishmanial infections.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KLRK1Humancutaneous leishmaniasis treatmentISOKlrk1 (Mus musculus)associated with lymphocytic choriomeningitisRGD 
Klrk1Ratcutaneous leishmaniasis treatmentISOKlrk1 (Mus musculus)associated with lymphocytic choriomeningitisRGD 
Klrk1Mousecutaneous leishmaniasis treatmentIMP associated with lymphocytic choriomeningitisRGD 

Objects Annotated

Genes (Rattus norvegicus)
Klrk1  (killer cell lectin like receptor K1)

Genes (Mus musculus)
Klrk1  (killer cell lectin-like receptor subfamily K, member 1)

Genes (Homo sapiens)
KLRK1  (killer cell lectin like receptor K1)


Additional Information