Lung immune responses during infection with the filarial nematode Litomosoides sigmodontis – crosstalk between lung and pleural cavity

Abstract text

Introduction

Recent advances in immunological studies have reinforced the existence of communication between tissues and organs, contributing to maintenance of host homeostasis but also to disease development. Helminth parasites are a great tool to investigate such inter-tissue communication because of their migration through different tissues and organs within their hosts.

Objectives

The filarial nematode Litomosoides sigmodontis (Ls) resides in the pleural cavity but has a transient lung stage between days 3-5 post infection and later during patency, microfilariae (MF) can accumulate in the lungs. However, pulmonary immune response during Ls infection are not well characterized so far. Here, we present a detailed overview of the ongoing immunological events within the lungs over the course of Ls infection. Further, we aimed to investigate whether immune responses within the lung can affect responses in the pleural cavity, the site of infection.

Materials & Methods

We used multi-color flow cytometry to investigate cellular composition, T cell and macrophage phenotypes as well as neutrophil-eosinophil kinetics in the lung and compared them side-by-side with the responses within the pleural cavity. ELISA and qPCR were performed to investigate cytokine/chemokine milieu and type 2 associated genes to obtain an overview of ongoing immune responses.

Results

We analyzed the early events (d3-5pi) of the lung response and found that BALB/c mice, but not semi-susceptible C57BL/6 mice that clear the infection shortly after the molt into adult filariae, upregulate IL-17A production by γδ T cells. This was associated with increased early lung tissue damage only seen in BALB/c mice. Depleting this early lung IL-17A resulted in significantly lower CD4+ T cell and eosinophil numbers and decreased production of the type 2 cytokines IL-5 and IL-13 in the pleural cavity d15pi. Currently we are deciphering the mechanisms by which pulmonary IL-17A regulates the pleural cavity response. Furthermore, with onset of microfilaremia, the lung displays an immune reaction similar to the pleural cavity, even though L4 and adult stages solely live in the pleural cavity. Interestingly, MF+ mice have a higher eosinophil frequency in the lung compared to MF- mice, indicating MF-dependent immune responses.

Conclusion

Our data suggests a crosstalk between the lung and the pleural cavity that supports the induction and maintenance of protective immune responses against filariae.