Research Topic

The Role of Gene Polymorphism in Modulating the Immune Responses against Tropical Infectious Diseases

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About this Research Topic

The immunological mechanisms involved in the pathogenesis of tropical and infectious diseases remain poorly understood. Several studies have attempted to elucidate the cellular and molecular events involved in the development of infectious diseases. Of all individuals exposed to pathogens, only a portion ...

The immunological mechanisms involved in the pathogenesis of tropical and infectious diseases remain poorly understood. Several studies have attempted to elucidate the cellular and molecular events involved in the development of infectious diseases. Of all individuals exposed to pathogens, only a portion develops the classic symptoms or evolves into severe diseases and functional sequels, suggesting that the genetic background of the host plays an important role in the susceptibility or resistance to infection.

Humans are continuously exposed to many infectious agents, and certain individuals have developed efficient responses to control and eliminate specific pathogenic infections, while others are unable to do so, and go on to develop diseases that sometimes may have serious consequences. Environmental factors partly explain such response heterogeneity, and host immunogenetic factors are involved in this process. Several genes encoding key molecules of the innate and adaptive immune responses have been implicated in the pathogenesis of infectious disorders, emphasizing the role of the genes of the major histocompatibility complex. The classical class I (HLA-A/B/C) and class II (HLA-DRB1/DQB1/DQA1) histocompatibility genes exhibit high diversity in worldwide populations and the diversity has probably been driven by pathogenic bioagents humans have fought with during evolution. The molecules encoded by these genes may modulate immune response depending on the residue variability exhibited at the HLA binding groove as well as by the residue variability of the presented pathogen peptide. In contrast to classical genes, the non-classical HLA class I genes (HLA-E/F/G) exhibit lesser gene/molecule variability in worldwide populations and their major role in the modulation of the cells of the innate and adaptive immune system, by interacting with leukocyte receptors, primarily inhibiting but also augmenting the immune responses. The best-studied of these genes is HLA-G, which inhibits the function of TCD4, TCD8, B, NK, and antigen-presenting cells. In contrast to other immune checkpoint molecules like PD-1 and CTLA-4 that inhibit only activated T lymphocytes, HLA-G has a much broader inhibitory effect.

Although there are several genes/molecules associated with the control of the immune response, this Research Topic will focus on how the diversity of HLA genes (promoter/coding and 3’ untranslated regulatory regions) may impact the susceptibility/protection to infectious diseases such as malaria, Chagas, Zika and other tropical infectious diseases. The variability at the regulatory regions may impact the magnitude of gene expression, since several variation sites at the promoter region may differentially impact the targeting of transcription factors; and the variability at the 3”UTR may impact microRNA binding. Additionally, variability at the coding region may impact HLA interaction with leukocyte receptors (for instance HLA-G with ILT2 and ILT4 receptors). Although the major focus will be on histocompatibility genes/molecules, all other immunomodulatory genes/molecules will be welcome.

We welcome authors to submit Review and Original Research articles focusing on new insights in the role of HLA polymorphisms in tropical infectious diseases, particularly regarding:

i) The understanding of the pathogenesis of each disease
ii) The development of an effective vaccine
iii) Mechanisms involved in the susceptibility or resistance to tropical and infectious diseases.


Keywords: Tropical infectious Diseases, HLA-G, Gene Polymorphism, Genetic Factors


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