The Polysaccharide Antibody Response after Streptococcus pneumoniae Vaccination Is Differentially Enhanced or Suppressed by 3,4-Dichloropropionanilide and 2,4-Dichlorophenoxyacetic Acid

Abstract

Propanil (3,4-dichloropropionanilide) and 2,4-D (2,4-dichlorophenoxyacetic acid) are commonly used herbicides that have toxic effects on the immune system. The present study determined the effect of exposure to these chemicals on the immune response to a bacterial vaccine. The antibody responses to the T-independent type 2 antigen, phosphorylcholine (PC) and the T-dependent antigen, pneumococcal surface protein A (PspA) were characterized in C57BL/6 mice after heat-killed Streptococcus pneumoniae (HKSP) immunization and single or mixture herbicide exposure. Propanil exposure significantly increased the number of PC-specific IgM, IgG2b, and IgG3 antibody-secreting B cells (ASC) in the spleen 4-6-fold over control animals in a dose-dependent manner. However, the number of ASC in the bone marrow and serum titers were comparable in control and propanil-treated mice. In contrast, 2,4-D exposure decreased the number of PC-specific IgM and IgG bone marrow ASC 2-3-fold from control animals. The decrease in bone marrow ASC in 2,4-D-treated mice corresponded to a 3-4-fold decrease in PC-specific IgM, IgG2b, and IgG3 serum titers compared to control mice. The number of ASC in the spleens of 2,4-D-treated mice was, however, comparable to control mice. The antibody response to PspA was not affected by any of the treatments. There were no mixture interactions between the two herbicides in any of the responses measured. These results characterize the primary PC-specific antibody response in the bone marrow, spleen, and serum after HKSP vaccination and herbicide exposure. The differential effects of propanil and 2,4-D on the antibody response to a bacterial vaccine demonstrate the potential of chemical exposure to augment or suppress immune responses to vaccines and infectious diseases.

The XX Sex Chromosome Complement is Required in Male and Female Mice for Enhancement of Immunity Induced by Exposure to 3,4‐Dichloropropionanilide

“…Several earlier reports have established the bone marrow as the primary source of serum antibodies 35 . These results suggest that propanil exposure does not alter the production of antibody in the bone marrow in FCG mice as had been previously demonstrated for wild type C57BL/6 mice 26 .…”

“…The number of ASC was normalized to 1×10 6 splenic B cells which were determined by flow cytometric analysis. Comparable fold increases were noted when normalized to whole spleen 26 .…”

“…Mice were treated intraperitoneally with propanil, 200 mg/kg, or vehicle on the day of vaccination with HKSP. The dose of propanil was based on previous studies that demonstrate an increase in the splenic antibody response to PC in vaccinated mice 26 .…”

“…Previous studies demonstrated that exposure to the chemical 3, 4-dichloropropionanilide (propanil) enhances the immune response to a heat-killed Streptococcus pneumoniae (HKSP) vaccine 26 . HKSP elicits a robust antibody response to the immunodominant T-independent type 2 polysaccharide phosphorylcholine (PC) 27 .…”

Prenatal cadmium exposure alters postnatal immune cell development and function

“…The vaccine was prepared as described by Salazar et al (Salazar et al , 2005). Briefly, S. pneumoniae strain R36A, was grown to mid-log phase in Todd-Hewitt broth (Difco) supplemented with 0.05% yeast extract (Difco) at 37 C in the presence of 10% CO 2 to an OD 600 of ~0.4.…”