RSV Bronchiolitis: Helminths as a Therapeutic Lead? A Synthesis of Four Windows of Action

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infants and can cause severe disease in older adults. Recent preventive advances exist, but access remains unequal worldwide. Helminthic therapy, mostly studied in autoimmune and allergic diseases, has been little explored for RSV. This narrative synthesis identifies four complementary windows of action. (1) Before birth: in mice, chronic maternal Heligmosomoides polygyrus inoculation reprograms the gut microbiota and protects offspring against RSV and influenza through indole-3-propionate (IPA) and type I interferon signaling, into adulthood. (2) Another indole pathway: Trichinella spiralis reduced pulmonary RSV load in mice, and a recent study links this species to indole-3-lactic acid (ILA) and AhR-dependent disease tolerance, shown in other models but not yet tested in RSV. (3) During active infection: helminth inoculation mobilizes monocytes that transiently reduce RSV load, and can durably reprogram lung-resident macrophages toward tolerance in an influenza model. (4) Immunomodulation: helminth-derived molecules and controlled Necator americanus inoculation in humans act on inflammation through Tregs/IL-10, CTLA-4 and IL-33 blockade. The evidence is mainly murine and heterogeneous, and these mechanisms have never been tested together. Version française : https://doi.org/10.5281/zenodo.23638600