Microfilaria-dependent thoracic pathology associated with eosinophilic and fibrotic polyps in filaria-infected rodents

Abstract

Background Pulmonary manifestations are regularly reported in both human and animal filariasis. In human filariasis, the main known lung manifestations are the tropical pulmonary eosinophilia syndrome. Its duration and severity are correlated with the presence of microfilariae. Litomosoides sigmodontis is a filarial parasite residing in the pleural cavity of rodents. This model is widely used to understand the immune mechanisms that are established during infection and for the screening of therapeutic molecules. Some pulmonary manifestations during the patent phase of infection with L. sigmodontis have been described in different rodent hosts more or less permissive to infection. Methods Here, the permissive Mongolian gerbil (Meriones unguiculatus) was infected with L. sigmodontis. Prevalence and density of microfilariae and adult parasites were evaluated. Lungs were analyzed for pathological signatures using immunohistochemistry and 3D imaging techniques (two-photon and light sheet microscopy). Results Microfilaremia in gerbils was correlated with parasite load, as amicrofilaremic individuals had fewer parasites in their pleural cavities. Fibrotic polypoid structures were observed on both pleurae of infected gerbils. Polyps were of variable size and developed from the visceral mesothelium over the entire pleura. The larger polyps were vascularized and strongly infiltrated by immune cells such as eosinophils, macrophages or lymphocytes. The formation of these structures was induced by the presence of adult filariae since small and rare polyps were observed before patency, but they were exacerbated by the presence of gravid females and microfilariae. Conclusions Altogether, these data emphasize the role of host-specific factors in the pathogenesis of filarial infections.

Unbalanced Arginine pathway and altered maturation of pleural macrophages in Th2-deficient mice during Litomosoides sigmodontis filarial infection

“…We recently described pathology of the visceral pleura (on the surface of the lung) in microfilaremic mice and gerbils (results from ( 12 , 44 ) summarized in Supplementary Table 1 ). In the current study, electron microscopy of the costal parietal pleura showed a smooth appearance in naive mice ( Figures 2A, B ) while the parietal pleura of infected WT mice revealed a strong inflammatory reaction with a high density of polyps ( Figures 2C, D ) of similar aspect to those observed in gerbils ( 44 ).…”

“…We recently described pathology of the visceral pleura (on the surface of the lung) in microfilaremic mice and gerbils (results from ( 12 , 44 ) summarized in Supplementary Table 1 ). In the current study, electron microscopy of the costal parietal pleura showed a smooth appearance in naive mice ( Figures 2A, B ) while the parietal pleura of infected WT mice revealed a strong inflammatory reaction with a high density of polyps ( Figures 2C, D ) of similar aspect to those observed in gerbils ( 44 ). These polyps were mainly observed along the intercostal space, at the edge of the ribs.…”

“…Slides were imaged on a Zeiss LSM880 confocal microscope as previously described ( 44 ). Acquisition was performed with a 32 channel Gallium arsenide phosphide (GaAsP) spectral detector using a 20× objective.…”

A noninvasive iRFP713 p53 reporter reveals dynamic p53 activity in response to irradiation and liver regeneration in vivo

“…Samples were then cleared for 45 minutes using Ce3D clearing solution prepared as described 51 and slices were transferred to glass slides, covered with Ce3D and coverslipped. Tiled images were acquired with a Zeiss LSM 880 NLO multiphoton microscope (Carl Zeiss, Germany) equipped with a 32-channel Gallium Arsenide Phosphide (GaAsP) spectral detector (Carl Zeiss, Germany) using 20×/1 NA water immersion objective lens as previously described 69 . Samples were either excited with a tunable pulsed laser in multiphoton mode (Discovery, Coherent, USA) set at 1000 nm, or with the combination of 405, 488 and 633 continuous wave lasers for single-photon operation.…”

Human filariasis—contributions of the Litomosoides sigmodontis and Acanthocheilonema viteae animal model

“…The presence of MF in particular has a significant impact on inflammation in the lung and pleural cavity. Recent studies by Fercoq et al ( 2020 ) demonstrated the formation of polyps on the pleura that consisted of up to 60% immune cells. The formation of these polyps which consisted mainly of CD3+ lymphocytes, CD68+ macrophages, and eosinophils correlated with the MF load (Fercoq et al 2020 ).…”