Identification of MHCII variants associated with chlamydial disease in the koala (Phascolarctos cinereus).

Quintin Lau,Joanna E Griffith,Damien P Higgins

doi:10.7717/peerj.443

Abstract

Chlamydiosis, the most common infectious disease in koalas, can cause chronic urogenital tract fibrosis and infertility. High titres of serum immunoglobulin G against 10 kDa and 60 kDa chlamydial heat-shock proteins (c-hsp10 and c-hsp60) are associated with fibrous occlusion of the koala uterus and uterine tube. Murine and human studies have identified associations between specific major histocompatibility complex class II (MHCII) alleles or genotypes, and higher c-hsp 60 antibody levels or chlamydia-associated disease and infertility. In this study, we characterised partial MHCII DAB and DBB genes in female koalas (n = 94) from a single geographic population, and investigated associations among antibody responses to c-hsp60 quantified by ELISA, susceptibility to chlamydial infection, or age. The identification of three candidate MHCII variants provides additional support for the functional role of MHCII in the koala, and will inform more focused future studies. This is the first study to investigate an association between MHC genes with chlamydial pathogenesis in a non-model, free-ranging species.

Highlights

Chlamydiosis, caused predominantly by Chlamydia pecorum and C. pneumoniae, is the most common infectious disease in koalas, causing proliferative conjunctivitis and/or chronic, fibrotic disease of the urogenital tract, which can lead to infertility and death (Griffith et al, 2013; Obendorf, 1983)
Consistent with Lau et al (2014), koalas had four to five DAB variants and one to two DBB variants identified per individual, and the DAB*19 and DAB*21 variants were found in a majority of koalas (96.8% and 98.9%, respectively), and were not included in analyses
Three new “genotype patterns” were identified from one-strand conformation polymorphism (OSCP) analyses, sequencing of these patterns showed that they comprised new combinations of previously identified major histocompatibility complex class II (MHCII) variants

Summary

Introduction

Chlamydiosis, caused predominantly by Chlamydia pecorum and C. pneumoniae, is the most common infectious disease in koalas, causing proliferative conjunctivitis and/or chronic, fibrotic disease of the urogenital tract, which can lead to infertility and death (Griffith et al, 2013; Obendorf, 1983). The murine IA genes are highly polymorphic MHCII genes that encode for membrane-bound molecules that bind specific exogenous antigens and present them to T lymphocytes (Balakrishnan & Adams, 1995; Kalish, 1995) These are orthologous to the human HLA-DQ α and β genes and, two human class II alleles, DQA1*0401 and DQB1*0402 (DQ4 phenotype), are associated with increased prevalence and magnitude of c-hsp antibody titres (Gaur et al, 1999), and a class II haplotype DR8 DQ4 is associated with presence of anti c-hsp antibodies (Betsou, Sueur & Orfila, 1999). A number of studies of Chlamydia trachomatis infection in women have identified associations between HLA (MHCII) genotypes and Chlamydia-associated pelvic inflammatory disease, cervicitis and tubal infertility (Cohen et al, 2003; Cohen et al, 2000; Ness et al, 2004)

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