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Splenic PGE 2 ‐releasing macrophages regulate Th1 and Th2 immune responses in mice treated with heat‐killed BCG
Author(s) -
Shibata Yoshimi,
Henriksen Ruth Ann,
Honda Ikuro,
Nakamura Reiko M.,
Myrvik Quentin N.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0605321
Subject(s) - biology , immune system , immunoglobulin e , spleen , immunology , cytokine , interleukin 4 , prostaglandin e , antibody , prostaglandin e2 , immunity , interferon gamma , interleukin 10 , endocrinology
Hosts infected with low doses of mycobacteria develop T helper cell type 1 (Th1) immunity, but at relatively higher doses, a switch to Th2 immunity occurs. Prostaglandin E 2 (PGE 2 ) is a proposed mediator of the Th1‐to‐Th2 shift of immune responses, and mycobacterial products induce PGE 2 ‐releasing macrophages (PGE 2 ‐MØ) in the mouse spleen in a dose‐dependent manner. Splenic PGE 2 ‐M Ø from Balb/c mice, given 0.01 or 1 mg heat‐killed (HK) Mycobacterium bovis bacillus Calmette‐Guerin (BCG) intraperitoneally (i.p.), were characterized by the ex vivo release of PGE 2 (>10 ng/10 6 cells), cytokine production, and expression of PGG/H synthase (PGHS)‐1, PGHS‐2, cytosolic PGE synthase (PGES), and microsomal PGES‐1. At Day 14 after the treatment, mice treated with 1 mg, but not 0.01 mg, BCG had increased levels of PGHS‐2 + PGE 2 ‐MØ, total serum immunoglobulin E (IgE), and serum IgG1 antibodies (Th2 responses) against heat shock protein 65 and purified protein derivative. Cultures of spleen cells isolated from these mice expressed interleukin (IL)‐4 and IL‐10 in recall responses. Treatment of mice receiving 1 mg BCG with NS‐398 (a PGHS‐2 inhibitor, 10 mg/kg i.p., daily) resulted in enhanced interferon‐γ (IFN‐γ) production with reduced IL‐4 and IL‐10 production in recall responses. This treatment also resulted in decreased total serum IgE levels. Treatment of C57Bl/6 mice with HK‐BCG (0.5 mg dose) also induced a mixture of Th1 and Th2 responses, although IFN‐γ production was markedly increased, and IL‐4 was decreased compared with Balb/c mice. Thus, our results indicate that by 14 days following treatment of mice with high doses of HK‐BCG, splenic PGE 2 ‐MØ formation is associated with a PGHS‐2‐dependent shift from Th1‐to‐Th2 immune responses.