Inconsistent MHC class II association in Beagles experimentally infected with Leishmania infantum

Area of Science:

• Veterinary Immunology
• Canine Infectious Diseases
• Molecular Genetics

Background:

• Clinical outcomes of Leishmania infantum infection in dogs vary significantly.
• Immune response genes are thought to influence the variability in clinical manifestations.
• Dog Leukocyte Antigen (DLA) class II genes are potential candidates influencing disease outcome.

Purpose of the Study:

• To test the hypothesis that MHC class II genes are associated with the disease outcome of experimental L. infantum infection in Beagles.
• To characterize DLA class II haplotypes in Beagles experimentally infected with L. infantum.
• To determine the association between DLA class II haplotypes and clinical score, serology, and parasite load.

Main Methods:

• Sequence-based typing of DLA class II haplotypes in Beagle dogs.
• Experimental infection of Beagles with L. infantum.
• Monitoring of clinical score, serology (anti-Leishmania antibodies), and quantification of L. infantum DNA in bone marrow.

Main Results:

• Limited DLA diversity was observed in the studied Beagles.
• Different DLA profiles were noted across various vaccine challenge studies.
• One haplotype (DLA-DRB1*001:02-DQA1*001:01-DQB1*002:01) was associated with increased anti-Leishmania antibodies in one model, but no other DLA associations were found with parasite load or clinical score.

Conclusions:

• The study found limited associations between DLA class II haplotypes and L. infantum infection outcomes in Beagles.
• Further investigation with a larger cohort is needed to confirm the potential role of the DLA-DRB1*001:02-DQA1*001:01-DQB1*002:01 haplotype.
• Genetic factors, beyond the investigated DLA class II haplotypes, likely play a significant role in L. infantum disease variability.