The XX Sex Chromosome Complement is Required in Male and Female Mice for Enhancement of Immunity Induced by Exposure to 3,4-Dichloropropionanilide - PubMed (original) (raw)

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

Ida Holásková et al. Am J Reprod Immunol. 2015 Aug.

Abstract

Problem: The chemical propanil enhances antibody responses to a heat-killed Streptococcus pneumoniae (HKSP) vaccine. The enhanced response is dependent on gonads in females, but independent of gonads in males. The sex differences in the immune response may be due to sexual differentiation of the immune system or sex chromosome complement.

Method of study: To test the hypothesis that the immune system is sexually differentiated, newborn C57BL/6 pups were treated with testosterone propionate (TP) or placebo. The role of sex chromosome complement was investigated using the 4-core genotypes (FCG) model of XXF and XYF gonadal females (ovaries), and XXM and XYM gonadal males (testes). For some experiments, mice were gonadectomized or sham gonadectomized. All mice were vaccinated with HKSP, treated with propanil, and the antibody response determined at day seven.

Results: Neonatal TP did not alter the response to HKSP. In FCG mice, propanil significantly enhanced the immune response in XXF females and XXM males, but not in XYF females or XYM males.

Conclusion: The immune system of females was not masculinized by neonatal TP treatment. Sex chromosome complement significantly contributes to the sexually dimorphic immune response after propanil exposure.

Keywords: Propanil; sex chromosome; sex differences.

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Figures

Figure 1

Neonatal TP treatment and immune response in female mice. All mice (males and females) were treated within 24 hours of birth with TP or the vehicle corn oil (CO). Vaginal smears were performed on the female offspring at 4 – 5 weeks of age and subsequently either sham-ovariectomized (Sham) or ovariectomized (GDX) at 6 weeks of age. At 10 weeks of age mice were either exposed i.p. to propanil (200 mg/kg) or the vehicle peanut oil and all mice vaccinated i.p. with 2×108 CFU HKSP. One week later the splenic PC-specific IgM and IgG antibody responses were determined.

Figure 2

Neonatal TP treatment does not alter the response to HKSP after propanil exposure. (A) Males. Vehicle (open bars), propanil (black bars) * P <0.02 (Tukey-Kramer); CO vs.CO propanil, TP vs. TP propanil. (B and C) Females. Vehicle (open bars), sham + propanil (black bars), GDX + propanil (gray bars). * P <0.05 (Tukey-Kramer); CO Sham vs CO Sham propanil, CO GDX vs. CO GDX propanil, TP Sham vs. TP Sham propanil. ** P <0.05 (ANOVA) CO Sham propanil vs. CO GDX propanil, TP Sham propanil vs. TP GDX propanil. # P < 0.05 (ANOVA) CO Sham vs. TP Sham, CO GDX vs. TP GDX.

Figure 3

XX sex chromosome complement is required for enhancement of the immune response to HKSP vaccination after exposure to propanil in females and males. XXF and XYF sham operated (Sham) or GDX (GDX) female mice and XYM and XXM sham operated (Sham) or GDX (GDX) male mice were treated as described in Figure 1. Values represent the mean ± SEM of ASC/1×106 B cells. Treatments: vehicle (open bars), sham + propanil (black bars), GDX + propanil (gray bars). (A) IgM and (B) IgG. * P < 0.05 (Tukey-Kramer) propanil exposed groups significantly different from matched vehicle treated group.

Figure 4

Statistically significant Main Effects (A) sex chromosomes (B) gonadal sex. (A) XX mice (open bars) significantly higher response than XY mice (hatched bars). *P <0.05. (B) XXF and XYF mice (open bars) significantly higher response than XXM and XYM males (hatched bars). (C) Significant two-way interaction of sex chromosomes and propanil in FCG mice. XX mice significantly higher response after exposure to propanil (black bars) compared to vehicle control (open bars), * P <0.05. (A, B, C) All values represent the least square means SEM of ASC/1×106 B cells. The SEM was < 5 for all groups.

References

1. Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008;8:737–744. - PMC - PubMed
1. Pennell LM, Galligan CL, Fish EN. Sex affects immunity. J Autoimmun. 2012;38:J282–J291. - PubMed
1. Quintero OL, Amador-Patarroyo MJ, Montoya-Ortiz G, Rojas-Villarraga A, Anaya JM. Autoimmune disease and gender: plausible mechanisms for the female predominance of autoimmunity. J Autoimmun. 2012;38:J109–J119. - PubMed
1. Klein SL. The effects of hormones on sex differences in infection: from genes to behavior. Neurosci Biobehav Rev. 2000;24:627–638. - PubMed
1. McClelland EE, Smith JM. Gender specific differences in the immune response to infection. Arch Immunol Ther Exp (Warsz) 2011;59:203–213. - PubMed

The XX Sex Chromosome Complement is Required in Male and Female Mice for Enhancement of Immunity Induced by Exposure to 3,4-Dichloropropionanilide - PubMed (original) (raw)