Role of CCR4 Ligands, CCL17 and CCL22, During Schistosoma mansoni Egg-Induced Pulmonary Granuloma Formation in Mice

Abstract

Controversy persists pertaining to the role of CCR4 ligands, namely CCL17 (or thymus and activation regulated chemokine; TARC) and CCL22 (or macrophagederived chemokine; MDC), in Th2-type cytokine-dominated responses in the lung. Accordingly, the present study addressed the relative role of each of these CC chemokines during an evolving pulmonary granulomatous response elicited by the intrapulmonary embolization of live Schistosoma mansoni eggs into S. mansoni-sensitized mice. CCL22 protein expression peaked at day 4, but CCL17 levels were not increased significantly at any time after egg challenge. CCR4 transcript and protein expression were highest at day 8 after egg embolization and CCR4 protein was prominently expressed in macrophages surrounding S. mansoni eggs. Systemic immunoneutralization of CCL22 from the time of egg injection into S. mansonisensitized mice for 8 days significantly decreased CCR4 protein expression, the eosinophil content, the overall size of the egg granuloma, and its hydroxyproline content. Whole lung levels of interferon-␥ were also significantly increased at day 8 in anti-CCL22-treated mice. The systemic immunoneutralization of CCL17 had a lesser effect on all of the granuloma parameters listed above, but this antibody treatment significantly decreased granuloma hydroxyproline content to a greater extent than the anti-CCL22 antibody treatment. In addition, the immunoneutralization of CCL17 significantly increased whole lung levels of interleukin (IL)-4, IL-5, IL-13, transforming growth factor-␤, IL-12, and tumor necrosis factor-␣ at day 8 after egg infusion. Thus, these studies demonstrate a major role for CCL22 and a lesser role for CCL17 during an evolving S. mansoni egg granuloma in the lung. Understanding the biology of chemotactic cytokines or chemokines and their receptors continues to challenge a number of researchers working in diverse fields such as inflammation, immune regulation, angiogenesis, virology, and lymphoid development.

Evaluation of the immunological effect of beta alanyl-l-histidine against Schistosoma mansoni antigens in rabbits

“…It also promoted liver regeneration in partially hepatectomized mice, which was shown in highly significant increases in weight, RNA content, and many hepatic proteins. The modulation of host immune response against SEA by L-carnosine could be comparable to the immune modulation of S. mansoni egg recorded by immunomodulators [42,43].…”

Severe Sepsis Exacerbates Cell-Mediated Immunity in the Lung Due to an Altered Dendritic Cell Cytokine Profile

“…mansoni egg-induced granulomas require the efficient and sequential recruitment of a series of immune effecter cells, including macrophages, 36 CD4 ϩ T cells, 37 and eosinophils. 38 These specific immune cells form a strong cellular barrier and sequester the S. mansoni eggs from the surrounding healthy tissue. We and others have shown that the cytokine/chemokine network plays a central role in the recruitment and activation of immune cells around the eggs.…”

Permanent up-regulation of regulatory T-lymphocytes in patients with head and neck cancer

“…+ lymphocytes with a Th2 phenotype and CD25 + regulatory T cells (55)(56)(57)(58)(59), but also by natural killer cells, dendritic cells and macrophages (60). CCR4 is supposed to be important for regulating immune balance (61).…”