Ascaris lumbricoides pseudocoelomic body fluid induces a partially activated dendritic cell phenotype with Th2 promoting ability in vivo.

Dendritic cells (DCs) matured with helminth-derived molecules that promote Th2 immune responses do not follow conventional definitions of DC maturation processes. While a number of models of DC maturation by Th2 stimuli are postulated, further studies are required if we are to clearly define DC maturation processes that lead to Th2 immune responses. In this study, we examine the interaction of Th2-inducing molecules from the parasitic helminth Ascaris lumbricoides with the maturation processes and function of DCs. Here we show that murine bone marrow-derived DCs are partially matured by A. lumbricoides pseudocoelomic body fluid (ABF) as characterised by the production of IL-6, IL-12p40 and macrophage inflammatory protein 2 (MIP-2) but no enhanced expression of cluster of differentiation (CD)-14, T-cell co-stimulatory markers CD80, CD86, CD40, OX40L and major histocompatibility complex class II was observed. Despite these phenotypic characteristics, ABF-stimulated DCs displayed the functional hallmarks of fully matured cells, enhancing DC phagocytosis and promoting Th2-type responses in skin-draining lymph node cells in vivo. ABF activated Th2-associated extracellular signal-regulated kinase-1 and nuclear factor-kB intracellular signalling pathways independently of toll-like receptor 4. Taken together, we believe this is the first paper to demonstrate A. lumbricoides murine DC-Th cell-driven responses shedding further light on DC maturation processes by helminth antigens.

Natural killer cells regulate T-cell proliferation during human parainfluenza virus type 3 infection.

Human parainfluenza virus type 3 (HPIV3) is a major respiratory pathogen in humans. Failure to induce immunological memory associated with HPIV3 infection has been attributed to inhibition of lymphocyte proliferation. We demonstrate that the inability of mixed lymphocytes to respond to virally infected antigen-presenting cells is due to an interleukin-2-dependent, nonapoptotic mechanism involving natural killer (NK) cells and their influence is exerted in a contact-dependent manner. These results suggest a novel regulatory mechanism for NK cells during HPIV3 infection, offering an explanation for viral persistence and poor memory responses.

Novel mechanism of immunosuppression by influenza virus haemagglutinin: selective suppression of interleukin 12 p35 transcription in murine bone marrow-derived dendritic cells.

Infection with influenza virus strongly predisposes an individual to bacterial superinfection, which is often the significant cause of morbidity and mortality during influenza epidemics. Little is known about the immunomodulating properties of the virus that lead to this phenomenon, but the effect of the viral components on the development of immune dendritic cells (DCs) may prove vital. In this study, activation of and cytokine secretion by bacterial lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) following treatment with the influenza virus major antigen haemagglutinin (HA) were examined. HA selectively inhibits the release of LPS-induced interleukin 12 (IL12) p70, which is independent of IL10 secretion. Suppression occurs at the transcriptional level, with selective inhibition of p35- and not p40-subunit mRNA expression. The downregulation of IL12 p70 by influenza HA is a novel and unexplored pathway that may be relevant in the predisposition to bacterial superinfection associated with influenza virus infections.