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Influence of HLA-DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a
Y H Sheen1,2, G Rajagopalan3, C M Snapper4
1Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
Abstract:
Asthma is independently associated with HLA-DR3 and increased risks of pneumococcal diseases. We aimed to determine whether HLA-DR polymorphism (HLA-DRB1*03), sensitization to house dust mite (HDM), or their interaction affects humoral immune responses to pneumococcal polysaccharide and protein antigens of intact pneumococci. Induction of serum titers of anti-pneumococcal polysaccharide and anti-surface protein IgM and IgG in response to immunization with intact pneumococci (Pn) serotype 14 was determined using humanized HLA-DR3 and DR2 transgenic mice. Transgenic mice were sensitized by injecting HDM and challenged with intranasal HDM. Mice were subsequently immunized with heat-killed Pn14 at day 24. Serum titers of anti-phosphorylcholine (PC) IgM and IgG, anti-pneumococcal polysaccharide, capsular type 14 (PPS14) IgM and IgG, and anti-pneumococcal surface protein A (PspA) IgG were measured. We included a total of 44 mice (22 DR3 and 22 DR2 mice) and half of mice in each group were sensitized with HDM (i.e. 22 HDM-sensitized and 22 control mice). HDM-sensitized mice, irrespective of HLA-DR polymorphism, had significantly lower humoral immune responses. HLA-DR3 mice, irrespective of HDM sensitization, elicited a significantly lower anti-PC IgG response. In contrast, the anti-PspA IgG response was higher in DR3 relative to DR2 mice. The effect of HDM sensitization on lowering humoral immune responses to Pn14 was observed in DR3 mice regardless of the nature of the antigen, whereas such decreases were observed only for the anti-PPS14 IgG and anti-PC IgM responses in DR2 mice. HDM sensitization lowered humoral immune responses to intact pneumococcus and this effect was significantly modified by the HLA-DR polymorphism.
Insights
House dust mite sensitization impairs immune responses to pneumococcus, particularly in individuals with HLA-DR3. This highlights how genetic factors and environmental exposures interact to influence susceptibility to bacterial infections like pneumococcal disease.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Asthma is linked to HLA-DR3 and increased pneumococcal disease risk.
- Understanding the interplay between HLA-DR polymorphism, house dust mite (HDM) sensitization, and immune response to pneumococcus is crucial.
Purpose of the Study:
- To investigate how HLA-DR polymorphism (specifically HLA-DRB1*03), HDM sensitization, or their interaction affects humoral immunity against pneumococcal antigens.
- To assess immune responses to pneumococcal polysaccharide and protein antigens in HLA-DR3 and HLA-DR2 transgenic mice.
Main Methods:
- Humanized HLA-DR3 and DR2 transgenic mice were used.
- Mice were sensitized with HDM and challenged intranasally.
- Humoral immune responses (IgM and IgG titers) to intact pneumococcus serotype 14, pneumococcal polysaccharide (PPS14), and pneumococcal surface protein A (PspA) were measured after immunization.
Main Results:
- HDM sensitization significantly reduced humoral immune responses to pneumococcus in all mice, regardless of HLA-DR type.
- HLA-DR3 mice showed lower anti-phosphorylcholine (PC) IgG responses but higher anti-PspA IgG responses compared to DR2 mice.
- HDM's suppressive effect on immune responses was more widespread in DR3 mice than in DR2 mice, indicating a significant interaction with HLA-DR polymorphism.
Conclusions:
- HDM sensitization generally lowers humoral immunity to pneumococcus.
- HLA-DR polymorphism significantly modifies the impact of HDM sensitization on immune responses to pneumococcal antigens.
- Findings suggest a complex interplay between genetic predisposition (HLA-DR3) and environmental factors (HDM) in modulating susceptibility to pneumococcal infections.
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