Localized Th1-, Th2-, T Regulatory Cell-, and Inflammation-Associated Hepatic and Pulmonary Immune Responses inAscaris suum-Infected Swine Are Increased by Retinoic Acid

Abstract

Pigs infected with Ascaris suum or controls were given 100 g (low-dose) or 1,000 g (high-dose) all-trans retinoic acid (ATRA)/kg body weight in corn oil or corn oil alone per os on days after inoculation (DAI) ؊1, ؉1, and ؉3 with infective eggs. Treatment with ATRA increased interleukin 4 (IL4) and IL12p70 in plasma of infected pigs at 7 DAI and augmented bronchoalveolar lavage (BAL) eosinophilia observed at 7 and 14 DAI. To explore potential molecular mechanisms underlying these observations, a quantitative real-time reverse transcription (RT)-PCR array was used to examine mRNA expression in tissue. Ascaris-infected pigs had increased levels of liver mRNA for T-helper-2 (Th2)-associated cytokines, mast cell markers, and T regulatory (Treg) cells, while infected pigs given ATRA had higher IL4, IL13, CCL11, CCL26, CCL17, CCL22, and TPSB1 expression. Gene expression for Th1-associated markers (IFNG, IL12B, and TBX21), the CXCR3 ligand (CXCL9), IL1B, and the putative Treg marker TNFRSF18 was also increased. Expression of IL4, IL13, IL1B, IL6, CCL11, and CCL26 was increased in the lungs of infected pigs treated with ATRA. To determine a putative cellular source of eosinophil chemoattractants, alveolar macrophages were treated with IL4 and/or ATRA in vitro. IL4 induced CCL11, CCL17, CCL22, and CCL26 mRNA, and ATRA increased the basal and IL4-stimulated expression of CCL17 and CCL22. Thus, ATRA augments a diverse Th1-, Th2-, Treg-, and inflammation-associated response in swine infected with A. suum, and the increased BAL eosinophilia may be related to enhanced induction of eosinophil chemokine activity by alveolar macrophages.

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis

“…2 Survival curve after induction of AIH, followed by prophylactic and therapeutic treatment with Asc. *p<0.05 compared to control group Dawson et al 2009). Their components could act to induce a Treg response in the liver or lymphoid organs through IL-10 production, and consequently improve liver tissue and serum markers.…”

“…Ascaris lumbricoides infections in endemic regions were associated with a highly polarized Th2 cytokine response . Generation of regulatory T cells (Tregs) in the liver and blood was observed during ascariasis (Matera et al 2008;Dawson et al 2009). The anti-A.…”

The Pathogenicity of an EntericCitrobacter rodentiumInfection Is Enhanced by Deficiencies in the Antioxidants Selenium and Vitamin E

“…cDNA for gene expression studies was prepared from colonic tissue (13). Briefly, 50 ng cDNA per reaction was used for quantitative PCR (qPCR) amplification with a commercially available kit (Abgene, Rochester, NY), and amplification was measured on an ABI7700 instrument (Applied Biosystems, Foster City, CA).…”

Transcriptional immune response in mesenteric lymph nodes in pigs with different levels of resistance to Ascaris suum

“…CCL17 is a chemokine produced by epithelial cells and dendritic cells which binds to Th2 cells (Hartl et al 2009). Dawson et al (2009) reported significant higher CCL17 expression on day 7 PI in liver tissue of pigs given retinoic acid and infected with A. suum than in uninfected controls; however, to our knowledge, a significant upregulation due to A. suum infection alone has not previously been demonstrated for this chemokine. In agreement with our results, Geiger et al (2013) found infection with helminths was associated with higher CCL17 concentration in human serum and Burke et al (2011) reported higher CCL17 expression in lungs of Schistosoma japonicum-infected mice compared with uninfected controls.…”