The role of HLA‐G in parasitic diseases

Abstract

Little attention has been devoted to the role of HLA-G gene and molecule on parasitic disorders, and the available studies have focused on malaria, African and American trypanosomiasis, leishmaniosis, toxoplasmosis and echinococcosis. After reporting a brief description regarding the role of the cells of innate and adaptive immune system against parasites, we reviewed the major features of the HLA-G gene and molecule and the role of HLA-G on the major cells of immune system. Increased levels of soluble HLA-G (sHLA-G) have been observed in patients presenting toxoplasmosis and in the active phase of echinococcosis. In addition, increased sHLA-G has also been associated with increased susceptibility to malaria and increased susceptibility to develop human African trypanosomiasis (HAT). In contrast, decreased membrane-bound HLA-G has been reported in placenta of patients infected with Plasmodium falciparum and in heart and colon of patients presenting Chagas disease. The 3' untranslated region of the HLA-G gene has been the main focus of studies on malaria, HAT and Chagas disease, exhibiting distinct patterns of associations. Considering that HLA-G is an immune checkpoint molecule, inhibiting the activity of several cells of the immune system, the excessive neoexpression and the increased sHLA-G levels together with the decreased constitutive tissue expression of membrane-bound HLA-G may be detrimental to the host infected with parasite agents.

Balancing Selection atHLA-GModulates Fetal Survival, Preeclampsia and Human Birth Sex Ratio

“…In agreement with this scenario, ancestral fetal 10 HLA-G haplotypes showed associations with preeclampsia and stillbirths in our series, thereby supporting their disadvantage in modern environments. Furthermore, high HLA-G expression is, however, associated with higher implantation rates (30) and uneventful pregnancies as presented here, but might confer an increased risk of offspring to malaria and other parasitic infections (31,32). These mechanisms might be in part mediated by the fms-like tyrosine kinase 1 (FLT1) gene, as our results link balancing selection of HLA- 15 G regulatory haplotypes also to asymmetry for placental FLT1 expression.…”

Co-infecção Plasmodium falciparum e Schistosoma haematobium: papel dos genes HLA não-clássicos de classe I (HLA-G, -E e -F) na suscetibilidade à malária

“…On the other hand, HLA non-classical class I genes have not been studied yet. Nevertheless, studies in other parasitic diseases found HLA-G 3' UTR polymorphisms exhibiting distinct patterns of associations with both Human African Trypanosomiasis (HAT) and American Trypanosomiasis (Chagas disease) Dias et al 2015;Sabbagh et al 2018).…”

“…HLA-E and HLA-F are the most conserved ones, exhibiting 27 and 30 alleles, respectively, accompanied by HLA-G with 60 different alleles (IPD-IMGT/HLA v.3.32.0, 2018-04-16) (Robinson et al 2015). HLA-G, -E, and -F show a restricted expression pattern and are important regulators of the immune system cells (Carosella et al 2015;Persson et al 2017;Sabbagh et al 2018). Since HLA-G, HLA-E, HLA-F and HLA-C molecules are simultaneously expressed at the fetal-maternal interface, these molecules have been associated with immune tolerance towards the semi-allogeneic fetus (Kovats et al 1990;Ishitani et al 2003Ishitani et al , 2006.…”

“…where the HLA-G 3' UTR polymorphisms exhibited distinct patterns of associations with both HAT and Chagas disease Dias et al 2015;Sabbagh et al 2018).…”

“…falciparum malaria clinical phenotypes focused on the HLA-G 3' UTR segment (Sabbagh et al , 2018Garcia et al 2013). Thus, except the study conducted by Gineau et al (2016) that evaluated the association of variable sites in the entire HLA-G (including 5' UR, coding The 14 bp Indel, belonging to HLA-G 3' UTR, has been extensively studied, and numerous genetic associations were reported between this variant and disease mordidity or susceptibility (Wang et al 2013;Zhang et al 2014;Fan et al 2014Fan et al , 2017Ge et al 2014;Catamo et al 2015;Kim et al 2015;Lee et al 2015;Li et al 2015;Pabalan et al 2015;Coelho et al 2016;Shi et al 2017;de Almeida et al 2018).…”