TGFβ depletion does neither modulate acute E. coli-induced inflammatory immune responses nor impair the protective effect by chronic filarial infection.

TGFβ is an anti-inflammatory molecule that suppresses pro-inflammatory immune responses. Previously, we demonstrated that chronic filarial infection has a beneficial impact on Escherichia coli-induced sepsis. In the present study, we investigated whether this protective effect is dependent on TGFβ signaling and whether depletion of TGFβ before E. coli challenge alters the early course of sepsis per se. In vivo depletion of TGFβ before E. coli challenge did not alter levels of pro-inflammatory cytokines/chemokines and did neither increase the bacterial burden nor worsen E. coli-induced hypothermia six hours post E. coli challenge. Similarly, in the co-infection model, despite TGFβ depletion, mice infected with the filarial nematode Litomosoides sigmodontis exhibited milder E. coli-induced hypothermia, reduced bacterial load and pro-inflammatory immune responses. Thus, we conclude that TGFβ is not essentially modulating the initial pro-inflammatory phase during sepsis and that the protective effect of a chronic filarial infection against sepsis is independent of TGFβ signaling.