Microbial (co)infections: Powerful immune influencers
Fig 2
Examples of immunomodulation through infection-mediated IFN-I.
IFN-I display high modulatory potential as illustrated by their capacity to positively or negatively modulate infectious or autoimmune diseases and to shape the functions of innate and adaptive immune cells. (A) DCs present parasitic antigens to T cells, which induces cell migration to the brain and proinflammatory cytokine production causing cerebral malaria. LDV infection induces IFN-I production by pDC. Released IFN-I causes a quantitative and qualitative defect in DC and, consequently, a decreased inflammatory response leading to the protection against cerebral malaria. (B) Bacterial ligands stimulate NF-κB translocation leading to TNF-α production. TNF stimulates bacterial phagocytosis by macrophages. Phage RNA triggers IFN-I production through TLR3-mediated TRIF signaling. IFN-I inhibits TNF production and bacterial phagocytosis and prevents infection clearance. (C) Rotavirus RNA induces IFN-I by pDC through TLR7/MDA5 signaling. IFN-I induces lymphocyte activation, B cells up-regulate MHC-I expression and present autoantigens to CD8+ T cells, which, in turn, produce proinflammatory molecules and cause death of pancreatic β cells. (IFN-I production and modulatory functions are presented in green). DC, dendritic cell; IFN-I, type I interferon; LDV, lactate dehydrogenase-elevating virus; pDC, plasmacytoid DC; TNF, tumor necrosis factor.