Phagocyte-specific S100 proteins in the local response to theEchinococcus granulosuslarva

Abstract

SUMMARYInfection by larvalEchinococcus granulosusis usually characterized by tight inflammatory control. However, various degrees of chronic granulomatous inflammation are also observed, reaching a high point in infection of cattle by the most prevalent parasite strain worldwide, which is not well adapted to this host species. In this context, epithelioid and multinucleated giant macrophages surround the parasite, and the secreted products of these cells often associate with the larval wall. The phagocyte-specific S100 proteins, S100A8, S100A9 and S100A12, are important non-conventionally secreted amplifiers of inflammatory responses. We have analysed by proteomics and immunohistochemistry the presence of these proteins at theE. granulosuslarva-host interface. We found that, in the context of inflammatory control as observed in human infections, the S100 proteins are not abundant, but S100A9 and S100A8 can be expressed by eosinophils distal to the parasite. In the granulomatous inflammation context as observed in cattle infections, we found that S100A12 is one of the most abundant host-derived, parasite-associated proteins, while S100A9 and S100A8 are not present at similarly high levels. As expected, S100A12 derives mostly from the epithelioid and multinucleated giant cells. S100A12, as well as cathepsin K and matrix metalloproteinase-9, also expressed byE. granulosus-elicited epithelioid cells, are connected to the Th17 arm of immunity, which may therefore be involved in this granulomatous response.

Granulomatous responses in larval taeniid infections

“…Cattle hydatids usually show poor vitality and important levels of local inflammation, presumably because most cases studied correspond to parasite species other than E. ortleppi , the former “cattle strain” of E. granulosus . The local response to cattle infection is in most cases a typical granuloma, similar to that described above for pig infections. However, one report describes the so‐called advanced lesions featuring strong eosinophil infiltration between the epithelioid rim and the LL and degenerating parasites …”

“…Established infections in sheep as well as in humans are in most cases immediately surrounded by a mostly acellular collagen capsule; areas of necrosis between the capsule and the LL can occur. In addition, local infiltration by lymphocytes (T and B), macrophages and, in cases, eosinophils is usually observed, but this is always distal to the parasite.…”

“…Epithelioid cells can express nitric oxide synthase isoforms, as found in the tuberculosis granuloma . Epithelioid cells in E. granulosus infections secrete S100A12, a protein thought to be a direct effector against helminths in nematode systems, as well as resorptive proteinases …”

“…infection is deduced from histological results obtained at a later phase. 72 Established infections in sheep as well as in humans are in most cases immediately surrounded by a mostly acellular collagen capsule [73][74][75][76][77][78][79] ; areas of necrosis between the capsule and the LL can occur.…”

“…34 Human and sheep infections (typically). [73][74][75][76][77][78][79]99 Pig infections (cases). 80 Cattle infections (rare) 81 "Late" "uncomplicated" infections in paca 86…”