IL-10R blockade during chronic schistosomiasis mansoni results in the loss of B cells from the liver and the development of severe pulmonary disease

• Published in: PLoS pathogens Vol. 8; no. 1; p. e1002490
• Main Authors: Fairfax, Keke C, Amiel, Eyal, King, Irah L, Freitas, Tori C, Mohrs, Markus, Pearce, Edward J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2012; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies, Helminth - genetics; Antibodies, Helminth - immunology; Antibodies, Helminth - metabolism; Biology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Chronic Disease; Chronic illnesses; Development and progression; Health aspects; Host-parasite relationships; Immune response; Immune system; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Immunoglobulin G - metabolism; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-10 - metabolism; Liver; Liver - immunology; Liver - metabolism; Liver - parasitology; Liver - pathology; Liver Cirrhosis - genetics; Liver Cirrhosis - immunology; Liver Cirrhosis - metabolism; Liver Cirrhosis - parasitology; Lung diseases; Lung Diseases, Parasitic - genetics; Lung Diseases, Parasitic - immunology; Lung Diseases, Parasitic - metabolism; Lung Diseases, Parasitic - parasitology; Lung Diseases, Parasitic - pathology; Mice; Mice, Inbred BALB C; Mice, Knockout; Mortality; Physiological aspects; Plasma Cells - immunology; Plasma Cells - metabolism; Plasma Cells - pathology; Receptors, Interleukin-10 - antagonists & inhibitors; Receptors, Interleukin-10 - genetics; Receptors, Interleukin-10 - immunology; Receptors, Interleukin-10 - metabolism; Schistosoma mansoni; Schistosomiasis; Schistosomiasis mansoni - genetics; Schistosomiasis mansoni - immunology; Schistosomiasis mansoni - metabolism; Schistosomiasis mansoni - pathology; United States
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1002490

In schistosomiasis patients, parasite eggs trapped in hepatic sinusoids become foci for CD4+ T cell-orchestrated granulomatous cellular infiltrates. Since the immune response is unable to clear the infection, the liver is subjected to ongoing cycles of focal inflammation and healing that lead to vascular obstruction and tissue fibrosis. This is mitigated by regulatory mechanisms that develop over time and which minimize the inflammatory response to newly deposited eggs. Exploring changes in the hepatic inflammatory infiltrate over time in infected mice, we found an accumulation of schistosome egg antigen-specific IgG1-secreting plasma cells during chronic infection. This population was significantly diminished by blockade of the receptor for IL-10, a cytokine implicated in plasma cell development. Strikingly, IL-10R blockade precipitated the development of portal hypertension and the accumulation of parasite eggs in the lungs and heart. This did not reflect more aggressive Th2 cell responsiveness, increased hepatic fibrosis, or the emergence of Th1 or Th17 responses. Rather, a role for antibody in the prevention of severe disease was suggested by the finding that pulmonary involvement was also apparent in mice unable to secrete class switched antibody. A major effect of anti-IL-10R treatment was the loss of a myeloid population that stained positively for surface IgG1, and which exhibited characteristics of regulatory/anti-inflammatory macrophages. This finding suggests that antibody may promote protective effects within the liver through local interactions with macrophages. In summary, our data describe a role for IL-10-dependent B cell responses in the regulation of tissue damage during a chronic helminth infection.