Trends in Genetics
ReviewHost–pathogen interactions revealed by human genome-wide surveys
Section snippets
Contribution of human genetic factors in host–pathogen interactions
Every infective episode, that may or may not cause disease, results from a microbe making contact with the host and the immune system making contact with the microbe. In this light, a detailed understanding of host–pathogen interactions will aid our efforts to understand the biology of infection, opening new avenues to vaccination and treatment. There is clear evidence that some individuals respond differently to infectious agents compared to others. Mortality from infection has been shown to
Understanding host–pathogen interactions
This section focuses on all GWAS leading to identification of host–pathogen interactions in infectious diseases where the pathogen has been clearly defined and where the genetic associations identified exceed the formal threshold for genome-wide significance.
Can host genetics help identifying causative pathogen triggers?
An infective trigger is suspected for several diseases thought to be primarily autoimmune or inflammatory, such as type-1 diabetes, systemic lupus erythematosus, IBD, KD and others, many hinted at by the nature of the pathogen-recognition genes associated with these diseases. However, because an infectious trigger has not yet been identified, the concept remains speculative. Here, we use two of these diseases (IBD and KD 63, 64) as case studies and discuss these in more detail.
Future approaches to characterize host–pathogen interactions
Despite the recognized contribution of the GWAS approach to the field of infectious diseases, only a fraction of the heritable component of human infection has been explained by the GWAS approach, indicating that a substantial proportion of other relevant host–pathogen interactions remain to be identified [76]. Because the current GWAS method of using surrogate markers imperfectly captures information for these sequence variants, the challenge to be solved (so that more of the heritable
Concluding remarks
GWAS of human infectious diseases have revealed or retrospectively confirmed the identity of specific host–pathogen interacting molecules at unprecedented levels of accuracy and statistical confidence (Figure 1). Future research should now aim at discerning the precise molecular mechanisms of each interaction, first by identifying the respective causative mutations, and then by ex vivo biological assays, thus providing new targets for the development of potential vaccines or therapies. Once
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2016, Ticks and Tick-borne DiseasesCitation Excerpt :Individual differences in the ability of the host innate immune system to efficiently suppress the development of disease are to a large extent predetermined genetically. Many human genes that are involved in the protection against different viral diseases have previously been detected in different populations worldwide (Chapman and Hill, 2012; Khor and Hibberd, 2012). However, human genetic predisposition to tick-borne encephalitis (TBE) has been poorly studied.
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