Genetic risk factors for human susceptibility to infections of relevance in dermatology

Abstract

BACKGROUND: In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection. Keywords: Dermatology; Infection; Polymorphism, genetic Resumo: INTRODUÇÃO: Durante a era pré-microbiológica, era comum a visão de que doenças, hoje sabidamente infecciosas, eram hereditárias. Com a descoberta dos microorganismos e seu papel na patogênese de diversas patologias, chegou-se a propor que a exposição ao patógeno era condição suficiente para explicar infecção. Hoje, está claro que infecção é o resultado de uma complexa interação entre patógeno e hospedeiro, dependendo portanto, em última análise, do make-up genético de ambos os organismos. A dermatologia oferece diversos exemplos de doenças infecciosas em diferentes graus de entendimento de suas bases moleculares. Nesta revisão, resumimos os principais avanços na direção da dissecção do componente genético controlando suscetibilidade do ser humano a doenças infecciosas de importância na dermatologia. Doenças amplamente estudadas, como a hanseníase e a leishmaniose, são discutidas sob o ponto de vista da genética tanto do hospedeiro quanto do patógeno. Outras, como micobacterioses raras, micoses e sífilis, são apresentadas como boas oportunidades para pesquisa na área de genética de infecção.

Differentiation of mucosal lesions in mucocutaneous leishmaniasis and paracoccidioidomycosis

“…A higher susceptibility to these diseases in males, apart from possible differences in exposure and in risk factors, could be related to the influence of androgen hormones in their pathogenicity, as suggested in previous studies. This could also partially explain a higher occurrence in adults [ 13 , 14 ]. Furthermore, children and young adults with paracoccidioidomycosis may be more likely to present the acute/subacute form of the disease, which affects mainly the lymphohematopoietic system, with a lower involvement of mucocutaneous regions [ 15 , 16 ].…”

Primary cutaneous histoplasmosis in an immunocompromised patient with long-standing rheumatoid arthritis

“…Today, it is clear that the infection is the result of a complex interaction between pathogen and host. 7 The patient presented lesions with no regional lymphadenopathy and no evidence of systemic involvement. Also, Histoplasma capsulatum was isolated and identified.…”

Genetic Susceptibility to Fungal Infections and Links to Human Ancestry

“…Now, challenge for biologists is to identify genetic components that predispose individuals to fungal infection. The study of genes will help to understand the relationship between genetic polymorphism and the cellular phenotype of host and pathogen ( Sardinha et al, 2011 ). Recent research outcomes aided by genomic sequencing point toward an interesting link between genetic predisposition to fungal infections and human ancestry.…”

“…Single nucleotide polymorphism (SNP) in key immune genes plays an important role in fungal infection affecting particular ancestral populations ( Hughes et al, 2008 ; Dominguez-Andres and Netea, 2019 ). Thus, with the availability of genetic information, we can study the mechanism behind host defense against the pathogen, susceptibility toward infection ( Sardinha et al, 2011 ), and also have an idea of how the pathogens are evolving and trying to adapt to their host environment through host-pathogen interactions.…”