Experimental Schistosoma japonicum-induced pulmonary hypertension

Abstract

Background Schistosomiasis, a major cause of pulmonary arterial hypertension (PAH) worldwide, is most clearly described complicating infection by one species, Schistosoma mansoni. Controlled exposure of mice can be used to induce Type 2 inflammation-dependent S. mansoni pulmonary hypertension (PH). We sought to determine if another common species, S. japonicum, can also cause experimental PH. Methods Schistosome eggs were obtained from infected mice, and administered by intraperitoneal sensitization followed by intravenous challenge to experimental mice, which underwent right heart catheterization and tissue analysis. Results S. japonicum sensitized and challenged mice developed PH, which was milder than that following S. mansoni sensitization and challenge. The degree of pulmonary vascular remodeling and Type 2 inflammation in the lungs was similarly proportionate. Cross-sensitization revealed that antigens from either species are sufficient to sensitize for intravenous challenge with either egg, and the degree of PH severity depended on primarily the species used for intravenous challenge. Compared to a relatively uniform distribution of S. mansoni eggs, S. japonicum eggs were observed in clusters in the lungs. Conclusions S. japonicum can induce experimental PH, which is milder than that resulting from comparable S. mansoni exposure. This difference may result from the distribution of eggs in the lungs, and is independent of which species is used for sensitization. This result is consistent with the clearer association between S. mansoni infection and the development of schistosomiasis-associated PAH in humans.

Parasitic lung diseases

“…Pulmonary schistosomiasis is more common from S. mansoni and Schistosoma japonicum . It was found that S. japonicum caused milder SchPAH than that caused by S. mansoni in an animal model, which was thought to be due to the uniform versus clustered distribution of eggs laid by S. mansoni and S. japonicum , respectively [ 45 ]. In an experimental study, S. japonicum resulted in 35-fold smaller granulomas than those caused by S. mansoni due to attenuated type 2 inflammation [ 45 ].…”

Experimental Schistosoma haematobium pulmonary hypertension

“…We previously observed that S. mansoni and japonicum effectively cross-sensitize for each other. 8 The observed relative inability of S. haematobium to crosssensitize for S. mansoni is paradoxical given these two species have a closer genetic relationship than S. japonicum. Investigating this incongruence further, possibly through in vitro systems, might shed light on mechanisms by which the immune system responds to Schistosoma and drives PAH.…”

“…FFPE tissue was stained for α-smooth muscle actin by published protocol. 8 Images were captured, the vascular media identified, the average outer and internal medial layer radii quantified, and the fractional medial thickness calculated as the radii difference divided by the external radius. We used the optical rotator 12 to estimate peri-egg granuloma volumes from hematoxylin and eosin-stained slides.…”

“…[5][6][7] Mice exposed to Schistosoma japonicum, endemic in Asia and the third most common species, also develop PH, albeit more mild than that induced by S. mansoni. 8 Here, we tested ifS. haematobium exposed mice can manifest PH, and evaluated the severity relative to other Schistosoma species.…”

Schistosomiasis-Associated Pulmonary Arterial Hypertension

“…In a study comparing experimental S. japonicum-induced PH to S. mansoni-induced PH, authors found that S. japonicum could cause PH in mice, but the severity was significantly less than that caused by S. mansoni. 45 If these species-specific phenotype differences are real clinically, it is largely unknown why these differences may occur and what the potential phenotype from S. haematobium infection is.…”