Spatial and temporal transcriptomics ofSchistosoma japonicum-induced hepatic granuloma formation reveals novel roles for neutrophils

Abstract

The severity of schistosome egg-induced hepatic granulomatous pathology depends markedly on the nature of the host immune responses. In this study, we used LMM and microarray analysis to compare gene expression profiles of histologically distinct zones within, and directly proximal to, hepatic granulomas that developed in C57BL/6 mice infected with Schistosoma japonicum. There was significant up-regulation of type-1, type-2, and type-17 immune-associated genes within the granuloma core (adjacent to eggs), followed by increased expression of type-2 and fibrotic genes at the outer zones of granulomas. Neutrophil-associated genes were also found to be expressed differentially in the core and at the peripheral zone of granulomas, present at 7 weeks p.i., demonstrating a significant role of neutrophils in S. japonicum granulomatous pathology. The release of NETs was observed microscopically in granulomas obtained from the livers of infected mice and when human neutrophils were incubated in vitro in the presence of S. japonicum eggs. These finding are the first to suggest a novel, dual role for neutrophils in the mediation of tissue damage and repair in S. japonicum egg-induced hepatic granulomatous lesions. Together, these results provide an overview of the local events occurring within the granuloma microenvironment.

Influence of Microbes on Neutrophil Life and Death

“…Although there seems to be an agreement that these structures trap microbes (Hermosilla et al, 2014), data that bear on the ability of NETs to kill parasites is at variance (Guimaraes-Costa et al, 2009; Hermosilla et al, 2014; McCoy et al, 2017). Regardless of the outcome for the microbe, release of cytotoxic neutrophil contents onto surrounding tissues either by degranulation, lysis, or NET formation can be detrimental to the host (Chuah et al, 2013; Hurrell et al, 2015). …”

Gaining biological perspectives from schistosome genomes

“…Such investigations provide new information as to how the parasite responds to changes in its microenvironment, particularly within the host, and how the host immune system reacts to the presence of the pathogen [27]. While many studies have sought to examine the response of the host to an active infection [28][29][30][31][32][33][34], this review will focus on the schistosome parasite itself and the transcriptional changes that allow it to survive long term within the host.…”

SjE16.7 activates macrophages and promotes Schistosoma japonicum egg-induced granuloma development

“…The formation of egg granulomas is a dynamic process involving several different cell populations and stages of cellular activation, differentiation and expansion. In addition, there are also species-specific differences, e.g., the egg granulomas induced by Schistosoma japonicum contains a higher ratio of neutrophils as compared with the granulomas induced by S. mansoni, which instead are dominated by eosinophils (Chuah et al, 2014b;Chuah et al, 2013). As an essential component of innate immunity, macrophages play critical roles in inflammation and host defense (Chuah et al, 2014a;Barron and Wynn 2011;Jenkins et al, 2005;Rodriguez-Acosta et al, 1992).…”