The role of the adaptor molecule STING during Schistosoma mansoni infection

• Published in: Scientific reports 2020-05, Vol.10 (1), p.7901-7901, Article 7901
• Main Authors: Souza, Cláudia, Sanches, Rodrigo C. O., Assis, Natan R. G., Marinho, Fábio V., Mambelli, Fábio S., Morais, Suellen B., Gimenez, Enrico G. T., Guimarães, Erika S., Castro, Tiago B. R., Oliveira, Sergio C.
• Format: Article
• Language: English
• Subjects: 631/250; 631/250/255/1715; 631/326; 631/326/417/2546; Alveoli; Animals; Bronchus; Deoxyribonucleic acid; Developing countries; Disease Models, Animal; DNA; DNA, Protozoan - immunology; Eggs; Embryo fibroblasts; Gastrointestinal Microbiome; Granuloma; Host-Pathogen Interactions - immunology; Humanities and Social Sciences; Immunity, Cellular; Immunity, Humoral; Infections; Inflammation; LDCs; Leukocytes (neutrophilic); Membrane Proteins - genetics; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mice; Mice, Knockout; Microbiota; multidisciplinary; Neutrophils; Nucleotidyltransferases - deficiency; Nucleotidyltransferases - metabolism; Organ Specificity - immunology; Parasites; Parasitic diseases; Public health; Reactive Oxygen Species - metabolism; Rodents; Schistosoma mansoni; Schistosoma mansoni - physiology; Schistosomiasis; Schistosomiasis mansoni - metabolism; Schistosomiasis mansoni - parasitology; Science; Science (multidisciplinary); Signal Transduction; Spleen; Survival; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-64788-6

Schistosomiasis is a human parasitic disease responsible for serious consequences for public health, as well as severe socioeconomic impacts in developing countries. Here, we provide evidence that the adaptor molecule STING plays an important role in Schistosoma mansoni infection. S. mansoni DNA is sensed by cGAS leading to STING activation in murine embryonic fibroblasts (MEFs). Sting −/− and C57BL/6 (WT) mice were infected with schistosome cercariae in order to assess parasite burden and liver pathology. Sting −/− mice showed worm burden reduction but no change in the number of eggs or granuloma numbers and area when compared to WT animals. Immunologically, a significant increase in IFN-γ production by the spleen cells was observed in Sting −/− animals. Surprisingly, Sting −/− mice presented an elevated percentage of neutrophils in lungs, bronchoalveolar lavage, and spleens. Moreover, Sting −/− neutrophils exhibited increased survival rate, but similar ability to kill schistosomula in vitro when stimulated with IFN-γ when compared to WT cells. Finally, microbiota composition was altered in Sting −/− mice, revealing a more inflammatory profile when compared to WT animals. In conclusion, this study demonstrates that STING signaling pathway is important for S. mansoni DNA sensing and the lack of this adaptor molecule leads to enhanced resistance to infection.