Immunity to Trichinella spiralis infection in vitamin A-deficient mice.

Abstract

SllmmaryVitamin A-deficient (A-) mice make strikingly poor IgG responses when they are immunized with purified protein antigens. Previously, we showed that A-T cells overproduce interferon 3' (IFN-3"), which then could inhibit interlenkin 4 (ID4)-stimalated B cell IgG responses. To determine if the altered IFN-3' regulation pattern and its immunological consequences would extend to a natural infection, we studied mice infected with the parasitic hdminth Trichinella spiralis. The course of the infection was similar in A-and A-sufficient (A +) mice. These mice did not differ with respect to newborn larvae/female/hour produced in the intestine, or muscle larvae burden 5 wk postinfection. They also did not differ in the intestinal worm expulsion rate until day 15, when A-mice still harbored parasites, whereas A § mice had cleared intestinal worms. Vitamin A deficiency reduced both the frequency of B lymphocytes secreting IgG1 antibodies to parasite antigens, and the bone marrow eosinophilia associated with hdminth infection. The cytokine secretion patterns in infected mice were consistent with these observations and with previous studies. Mesenteric lymph node cells from infected A-mice secreted siguificantly more IFN-3", and significantly less IL-2, IL-4, and IL-5 than infected A § controls. A-splenocytes secreted significantly more IFN-3', and equivalent amounts of IL-2, Ih-4, and IL-5 compared with A + controls. Interestingly, CD4-CDS-cells secreted the majority of the Ib4 produced in the spleen. The II.,2, Ib4, and Ib5 steady-state transcript levels correlated with secreted protein levels, but IFN-3' transcripts did not. Although they secreted more protein, A-cells contained fewer IFN-3" transcripts than A + cells. These results suggest two vitamin A-mediated regulation steps in IFN-3" gene expression: positive regulation of IFN-3' transcript levels, and negative regulation posttranscriptionally. The essentially unaltered outcome of T. spiralis infection in vitamin A-deficient mice probably reflects a balance between cellular and humoral responses. The IFN-3' overproduction might have a positive effect on the gut inflammatory response, but the decreased eosinophilia, cytokine production in mesenteric lymph node, and IgGl-secreting cell frequency might have a negative effect on T, spiralis immunity.

Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway

“…Memory T cells from vitamin A-deficient mice have been found to overproduce IFN-␥ and underproduce interleukin-4 (IL-4). 19 In contrast, administration of the active metabolite of vitamin A, retinoic acid (RA), has been reported to suppress memory cell IFN-␥ production and increase IL-4 secretion. 20 Later, it emerged that vitamin A can be metabolized into retinoic acid isomers with different ligand-receptor affinities: 9-cis retinoic acid, with a higher affinity for the RXR family, and all-trans retinoic acid (ATRA), with a higher affinity for the RAR family.…”

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

“…Ascarisinduced immunoglobulin E (IgE) production, localized eosinophilia, and increased ex vivo T-helper-2 (Th2) cytokine production indicated that immunity to Ascaris in pigs and humans is dominated by a Th2 response (2,11,15). It is well established that helminth infections coexist with malnutrition (25), and nutrient deficiencies and supplementation affect the immune responses to helminths (8,21,25,34,36). Conversely, helminth infection negatively affects nutrient status (23,25).…”

A Spectrum of Antibody (IgG, IgG1, IgM) Response in Mice Infected withTrichinella SpiralisTreated with L-Mimosine

“…Recent evidence shows that in Trichinella spiralis-infected mice there is a strong immune response, as measured by induction of serum antibody, activation of peritoneal mast cells, CD8+ and CD4+ T-cells and cytokines (29)(30)(31). IFN'Y, IL-4 and IL-5 reciprocally regulate the production of immunoglobulin isotypes.…”

“…The encysted larvae of T. spiralis present in the diaphragm from infected mice treated with L-mimosine were estimated on days 10,20,30,40,50 and 60 after infection, counting the cysts by trichinoscopy (x 50 magnification). Every week three mice from each group were sacrificed, by inhalation of CO z , and decapitated to estimate of number of cysts.…”