SOD3 suppresses early cellular immune responses to parasite infection

• Published in: Nature communications Vol. 15; no. 1; pp. 4913 - 10
• Main Authors: Li, Qilong, Lv, Kunying, Jiang, Ning, Liu, Tong, Hou, Nan, Yu, Liying, Yang, Yixin, Feng, Anni, Zhang, Yiwei, Su, Ziwei, Sang, Xiaoyu, Feng, Ying, Chen, Ran, Xu, Wenyue, Cui, Liwang, Cao, Yaming, Chen, Qijun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-06-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 38/88; 631/326/417/2546; 631/326/417/2547; 692/699/255/1629; 82/1; Animals; Female; Host-Parasite Interactions - genetics; Host-Parasite Interactions - immunology; Humanities and Social Sciences; Humans; Immune clearance; Immune response (cell-mediated); Immune system; Immunity, Cellular; Immunity, Innate; Infections; Innate immunity; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin 2; Interleukin-2 - genetics; Interleukin-2 - immunology; Interleukin-2 - metabolism; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Malaria; Malaria, Falciparum - immunology; Malaria, Falciparum - parasitology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; multidisciplinary; Neutrophils - immunology; Parasitemia; Parasitemia - immunology; Parasites; Plasmodium falciparum; Plasmodium falciparum - immunology; Protozoa; Science; Science (multidisciplinary); Superoxide dismutase; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; T-Lymphocytes - immunology; Vector-borne diseases; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-49348-0

Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both
Plasmodium falciparum
malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection.
Superoxide dismutase 3 is elevated in patients and animals infected by protozoan parasites such as
Plasmodium
. Here, Li et al. show that SOD3 expression is associated with experimental cerebral malaria and inhibition of host immune responses.