Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis

Abstract

Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analysis, and molecular biological technologies to explore the migration route of AC and the accompanying tissue damage in nonpermissive and permissive hosts. Our data indicated that, in nonpermissive host mouse, AC larvae migrated from intestinal wall to liver at 2 hours post-infection (hpi), from liver to lung at 4 hpi and then from lung to brain at 8 hpi. AC larval migration caused fatal lung injury (pneumonia) during acute and early infection phases, along with significant activation of Stat3/IL-6 signaling. In addition, AC induce sustained interstitial pneumonia in mouse and rat and pulmonary fibrosis only in rat during late infection phase. Moreover, during the early and late infection phases, Th2 cytokine expression and Stat3 and IL-6 signaling were persistently enhanced and myeloid macrophage cells were notably enriched in host lung, and administration of Stat3 and IL-6 inhibitors (C188-9 and LMT-28) attenuated AC infection-induced acute pneumonia in mice. Overall, we are the first to provide direct and systemic laboratory evidence of AC migration route in a nonpermissive host and report that infection with a high dose of AC larvae could result in acute and fatal pneumonia through Stat3/IL-6 signaling in mice. These findings may present a feasible to rational strategy to minimize the pathogenesis induced by AC.

ITRAQ-based quantitative proteomics analysis of forest musk deer with pneumonia

“…Among the cancer-related proteins, signal transducer and activator of transcription 3 (STAT3) has been well documented to be inflammation and immunity ( 62 – 64 ). Also, STAT3 served as a positive regulator of pneumonia induced by influenza virus H1N1 ( 65 ), Agiostrongylus cantonensis ( 66 ), and Mycoplasma pneumonia ( 67 ). Combined with these data, we supposed that dysregulated proteins related to amoebiasis and cancer might also function as crucial players in pneumonia, immune, and inflammation, suggesting the same or like immune response activity between pneumonia and amoebiasis or cancer.…”

CEBPα/miR-101b-3p promotes meningoencephalitis in mice infected with Angiostrongylus cantonensis by promoting microglial pyroptosis

“…A large number of cases have been documented in tropical and subtropical countries and regions, which are the natural epidemic foci for this infection, but, with the process of globalization, worldwide tourism and business exchanges have led to the appearance of Angiostrongyliasis in Europe, which is not a natural epidemic focus [ 2 ]. Rats are the permissive host of A. cantonensis in which larvae migrate from the brain to the lungs and then develop into adult worms [ 3 ]. On the contrary, human and mice are non-permissive hosts of A. cantonensis .…”