Tumor Necrosis Factor and Schistosoma mansoni egg antigen omega-1 shape distinct aspects of the early egg-induced granulomatous response

Infections by schistosomes result in granulomatous lesions around parasite eggs entrapped within the host tissues. The host and parasite determinants of the Schistosoma mansoni egg-induced granulomatous response are areas of active investigation. Some studies in mice implicate Tumor Necrosis Factor (TNF) produced in response to the infection whereas others fail to find a role for it. In addition, in the mouse model, the S. mansoni secreted egg antigen omega-1 is found to induce granulomas but the underlying mechanism remains unknown. We have recently developed the zebrafish larva as a model to study macrophage recruitment and granuloma formation in response to Schistosoma mansoni eggs. Here we use this model to investigate the mechanisms by which TNF and omega-1 shape the early granulomatous response. We find that TNF, specifically signaling through TNF receptor 1, is not required for macrophage recruitment to the egg and granuloma initiation but does mediate granuloma enlargement. In contrast, omega-1 mediates initial macrophage recruitment, with this chemotactic activity being dependent on its RNase activity. Our findings further the understanding of the role of these host- and parasite-derived factors and show that they impact distinct facets of the granulomatous response to the schistosome egg.

Tumor Necrosis Factor and Schistosoma mansoni egg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response

Infections by schistosomes result in granulomatous lesions around parasite eggs entrapped within the host tissues. The host and parasite determinants of the Schistosoma mansoni egg-induced granulomatous response are areas of active investigation. Some studies in mice implicate Tumor Necrosis Factor (TNF) produced in response to the infection whereas others fail to find a role for it. In addition, in the mouse model, the S. mansoni secreted egg antigen omega-1 is found to induce granulomas but the underlying mechanism remains unknown. We have recently developed the zebrafish larva as a model to study macrophage recruitment and granuloma formation in response to Schistosoma mansoni eggs. Here we use this model to investigate the mechanisms by which TNF and omega-1 shape the early granulomatous response. We find that TNF, specifically signaling through TNF receptor 1, is not required for macrophage recruitment to the egg and granuloma initiation but does mediate granuloma enlargement. In contrast, omega-1 mediates initial macrophage recruitment, with this chemotactic activity being dependent on its RNase activity. Our findings further the understanding of the role of these host- and parasite-derived factors and show that they impact distinct facets of the granulomatous response to the schistosome egg.

Periorbital Silicone Granulomatosis 30 Years after Acupuncture

Silicone-based compounds are commonly used in many medical applications, such as coatings for needles and syringes. Foreign body granulomas are a well-recognized complication of silicone exposure; however, they may be challenging to identify without a clear history. A 61-year-old female patient without prior history of periocular injections, filler, or surgery presented to our oculoplastic clinic with multiple periocular lesions. The patient subsequently underwent excisional biopsy of two prominent lesions, which were identified as granulomas on pathology. Further questioning revealed the cause to be facial acupuncture performed decades prior, and a subsequent targeted exam identified additional lesions at other needling sites. A third lesion was subsequently excised, and there was no recurrence at the last follow-up 3 months postsurgery. Acupuncture is an increasingly common but underrecognized source of silicone exposure and can present up to several decades after exposure as a chronic granulomatous response in a characteristic multifocal pattern.

Schistosoma mansoni eggs modulate the timing of granuloma formation to promote transmission

SUMMARYSchistosome eggs provoke the formation of granulomas, organized immune aggregates, around them. For the host, the granulomatous response can be both protective and pathological. Granulomas are also postulated to facilitate egg extrusion through the gut lumen, a necessary step for parasite transmission. We used zebrafish larvae to visualize the granulomatous response to Schistosoma mansoni eggs and inert egg-sized beads. Mature eggs rapidly recruit macrophages, which form granulomas within days. Egg-sized inert beads also induce granulomas rapidly, through a foreign body response. Strikingly, immature eggs evade macrophage recruitment altogether, revealing that the eggshell is immunological inert. These findings suggest that the parasite modulates the timing of granuloma formation to its advantage, inhibiting foreign body granuloma formation until it reaches the optimal maturation and location for extrusion. At this point, the parasite secretes specific antigens through the eggshell to trigger granulomas that might facilitate egg extrusion.

A Case of Cutaneous Tuberculosis Presenting with Generalized Xanthogranulomas

A 33-year-old male had a 22-year history of generalized xanthogranulomas but had a normal lipid profile. He also developed ulcerating plaques on his arm and back that were consistent with cutaneous tuberculosis on histopathologic and polymerase chain reaction PCR studies. In a normolipemic patient with generalized xanthogranulomas, a reactive granulomatous response of histiocytes to infection is explored since these share a common CD 14+ precursor with the macrophages that are vital in tuberculosis.