Characterization of theHistoplasma capsulatum-Induced Granuloma

Abstract

Rising rates of Histoplasma capsulatum infection are an emerging problem among the rapidly growing population of immune-compromised individuals. Although there is a growing understanding of systemic immunity against Histoplasma, little is known about the local granulomatous response, which is an important component in the control of infection. The focus of this article is the characterization of Histoplasma-induced granulomas. Five days after i.p. infection, infected macrophage appear in the liver and lung; however, no granulomas are apparent. Two days later, well-formed sarcoid granulomas are abundant in the lung and liver of infected mice, which contain all visible Histoplasma. Granulomas are dominated by macrophage and lymphocytes. Most of the Histoplasma and most of the apoptotic cells are found in the center of the lesions. We isolated liver granulomas at multiple time points after infection and analyzed the cellular composition, TCR gene usage, and cytokine production of granuloma-infiltrating cells. The lesions contain both CD4+ and CD8+ T cell subsets, and T cells are the primary source of IFN-γ and IL-17. The main source of local TNF-α is macrophage. Chemokines are produced by both infiltrating macrophage and lymphocytes. Dendritic cells are present in granulomas; however, T cell expansion seems to occur systemically because TCR usage is very heterogeneous even at the level of individual lesions. This study is the first direct examination of host cellular responses in the Histoplasma-induced granuloma representing the specific interface between host and pathogen. Our studies will allow further analysis of key elements of host Histoplasma interactions at the site of chronic infection.

Circulating IL-6, IL-17 and vitamin D in hepatocellular carcinoma: Potential biomarkers for a more favorable prognosis?

“…IL-17-secreting T H 17 cells play a protective role in certain bacterial infections, but they are primarily mediators of inflammation. Few studies have looked into the role of T H 17 cells in liver diseases; of these, there are reports of an elevated presence in patients with acute hepatic injury (Yasumi et al, 2007), in infection-induced hepatic granulomas (Heninger et al, 2006;Rutitzky et al, 2008), and in animal models of hepatic ischemia-reperfusion (Caldwell et al, 2005). A plethora of studies has investigated the association of circulating levels of IL-17 with individual liver diseases, including hepatitis B (Wang et al, 2011;Zhang et al, 2010), alcoholic hepatitis (Lemmers et al, 2009), autoimmune hepatitis (Zhao et al, 2011), and HCC (Wang et al, 2010;Zhang et al, 2009).…”

Granulomatous liver disease

“…Histoplasmosis is the most recognized fungal disease associated with hepatic granulomatous infection, though there are also reports of hepatic granulomatous disease associated with coccidiomycosis [3,24]. In the United States, histoplasmosis is endemic in the Ohio and Mississippi river valleys, with skin-test reactivity rates over 90% in endemic areas.…”

“…Foreign-body granulomas and lipogranulomas (which form in the setting of hepatic steatosis) are characterized by minimal infl ammatory involvement, consisting of a few macrophages [1]. Granulomas associated with infection are commonly understood to be a protective form of delayed-type hypersensitivity that leads to control of the expansion of infection [3]. The pathogens become isolated from further damaging interaction with the host.…”

“…However, only a few (about 1%) of those exposed to histoplasmosis develop symptomatic disease. The granuloma formation contains further growth and is associated with rapid clearance of the fungus [3]. Histoplasmosis-associated granulomas are dominated by macrophages (70% of the infl ammatory cell content) and lymphocytes; most Histoplasma (H. capsulatum) organisms and epithelioid cells are found in the center of the lesions [3].…”

Atividades in vitro e in vivo de microesferas biodegradáveis contendo leucotrieno B4 e/ou antígenos livres de células de Histoplasma capsulatum

“…Sendo assim, para o controle da infecção e geração de imunidade protetora são importantes IL-12 e IFN-γ para o desenvolvimento de uma resposta imune de padrão T "helper" 1 (Th1) (ZHOU et al, 1995;NEWMAN, 1999;DEEPE Jr, 2000;HENINGER et al, 2006). Além de realizarem a fagocitose, secreção de citocinas e a morte microbiana através da produção de intermediários reativos do oxigênio e NO, os macrófagos funcionam como células apresentadoras de antígeno (APCs) na resposta imune adaptativa mediada por células, e como células efetoras que controlam e matam patógenos intracelulares após ativação por citocinas (NEWMAN, 1999;DEEPE Jr, 2000).…”