No abstract

Trypanosoma vivax is a unicellular hemoparasite, and a principal cause of animal African trypanosomiasis (AAT), a vector-borne and potentially fatal livestock disease across sub-Saharan Africa. Previously, we identified diverse T. vivax-specific genes that were predicted to encode cell surface proteins. Here, we examine the immune responses of naturally and experimentally infected hosts to these unique parasite antigens, to identify immunogens that could become vaccine candidates. Immunoprofiling of host serum shows that one particular family (Fam34) elicits a consistent IgG antibody response. This gene family, which we now call Vivaxin, encodes at least 124 transmembrane glycoproteins that display quite distinct expression profiles and patterns of genetic variation. We focused on one gene (viv-β8) that encodes one particularly immunogenic vivaxin protein and which is highly expressed during infections but displays minimal polymorphism across the parasite population. Vaccination of mice with VIVβ8 adjuvanted with Quil-A elicits a strong, balanced immune response and delays parasite proliferation in some animals but, ultimately, it does not prevent disease. Although VIVβ8 is localized across the cell body and flagellar membrane, live immunostaining indicates that VIVβ8 is largely inaccessible to antibody in vivo. However, our phylogenetic analysis shows that vivaxin includes other antigens shown recently to induce immunity against T. vivax. Thus, the introduction of vivaxin represents an important advance in our understanding of the T. vivax cell surface. Besides being a source of proven and promising vaccine antigens, the gene family is clearly an important component of the parasite glycocalyx, with potential to influence host-parasite interactions.

No abstract

Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Currently there are limited effective therapeutics for pulmonary fibrosis due to an inadequate understanding of the pathogenic process and underlying mechanisms. We now show that in human idiopathic pulmonary fibrosis (IPF) the cytokine interleukin (IL)-25 positively correlates with periostin a marker human pulmonary fibrosis, and the presence of IL-13-producing type 2 innate lymphoid cells (ILC2) in the lung. Using murine models of pulmonary fibrosis we demonstrate an essential role for IL-25-elicited ILC2 in the generation of pulmonary collagen deposition, independent of an adaptive T cell response. Furthermore, we define a mechanism whereby IL-25 evokes ILC2 to induce pulmonary fibrosis via the alternative activation of macrophages in the lung. Collectively, we present a new innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2 that occurs independently of T cell-mediated antigen-specific immune responses. These results indicate that IL-25 and ILC2 are potential therapeutic targets for the treatment of human fibrotic diseases where antigen-independent damage responses may magnify the disease.