ILC2s Control Microfilaremia During Litomosoides sigmodontis Infection in Rag2-/- Mice

Abstract

Group 2 innate lymphoid cells (ILC2s) are inducers of type 2 immune responses, but their role during filarial infection remains unclear. In the present study, we used the <i>Litomosoides sigmodontis</i> rodent model of filariasis to analyze ILC2s during infection in susceptible BALB/c mice that develop a chronic infection with microfilaremia and semi-susceptible C57BL/6 mice that eliminate the filariae shortly after the molt into adult worms and thus do not develop microfilaremia. ILC2s (CD45⁺ Lineage^- TCRβ^- CD90.2⁺ Sca-1⁺ IL-33R⁺ GATA-3⁺) were analyzed in the pleural cavity, the site of <i>L. sigmodontis</i> infection, after the infective L3 larvae reached the pleural cavity (9 days post infection, dpi), after the molt into adult worms (30dpi) and during the peak of microfilaremia (70dpi). C57BL/6 mice had significantly increased ILC2 numbers compared to BALB/c mice at 30dpi, accompanied by substantially higher IL-5 and IL-13 levels, indicating a stronger type 2 immune response in C57BL/6 mice upon <i>L. sigmodontis</i> infection. At this time point the ILC2 numbers positively correlated with the worm burden in both mouse strains. ILC2s and GATA-3⁺ CD4⁺ T cells were the dominant source of IL-5 in <i>L. sigmodontis</i>-infected C57BL/6 mice with ILC2s showing a significantly higher IL-5 expression than CD4⁺ T cells. To investigate the importance of ILC2s during <i>L. sigmodontis</i> infection, ILC2s were depleted with anti-CD90.2 antibodies in T and B cell-deficient <i>Rag2^-/-</i> C57BL/6 mice on 26-28dpi and the outcome of infection was compared to isotype controls. <i>Rag2^-/-</i> mice were per se susceptible to <i>L. sigmodontis</i> infection with significantly higher worm burden than C57BL/6 mice and developed microfilaremia. Depletion of ILC2s did not result in an increased worm burden in <i>Rag2^-/-</i> mice, but led to significantly higher microfilariae numbers compared to isotype controls. In conclusion, our data demonstrate that ILC2s are essentially involved in the control of microfilaremia in <i>Rag2^-/-</i> C57BL/6 mice.