SUMMARY Following their discovery in the early 1970s, classical human leukocyte antigen (HLA) loci have been the prototypical candidates for genetic susceptibility to infectious disease. Indeed, the original hypothesis for the extreme variability observed at HLA loci (H-2 in mice) was the major selective pressure from infectious diseases. Now that both the human genome and the molecular basis of innate and acquired immunity are understood in greater detail, do the classical HLA loci still stand out as major genes that determine susceptibility to infectious disease? This review looks afresh at the evidence supporting a role for classical HLA loci in susceptibility to infectious disease, examines the limitations of data reported to date, and discusses current advances in methodology and technology that will potentially lead to greater understanding of their role in infectious diseases in the future.

SummaryGenetic epidemiology, including twin studies, provides robust evidence that genetic variation in human populations contributes to susceptibility to infectious disease. One of the major limitations of studies that attempt to identify the genes and mechanisms that underlie this susceptibility has been lack of power caused by small sample size. With the development of novel technologies, burgeoning information on the human genome, the HapMap project, and human genetic diversity, we are at the beginning of a new era in the study of the genetics of complex diseases. This review looks afresh at the epidemiological evidence that supports a role for genetics in susceptibility to infectious disease, examines the somewhat limited achievements to date, and discusses current advances in methodology and technology that will potentially lead to translational data in the future.

BackgroundRecurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies.ResultsMiddle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear.ConclusionsCorynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1154-3) contains supplementary material, which is available to authorized users.