Affiliation:
1. Diet, Genomics and Immunology Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, Maryland 20705
2. Experimental Transplantation and Immunology Branch, NCI, NIH, Bethesda, Maryland 20892
3. Clinical Center, NIH, Bethesda, Maryland 20892
Abstract
ABSTRACT
Pigs infected with
Ascaris suum
or controls were given 100 μg (low-dose) or 1,000 μg (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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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