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Strain differences in resistance to infection reversed by route of challenge: studies in blastomycosis
Abstract:
The inbred mouse strains C3H/HeJ and DBA/1J have been shown to represent the extremes of susceptibility and resistance, respectively, to pulmonary blastomycosis. This pattern was completely reversed when challenge was performed by the intraperitoneal route, whether a virulent or an attenuated strain of Blastomyces dermatitidis was utilized. By a third route (subcutaneous), the differences were insignificant. Inhibition of replication of blastomyces in vitro by macrophages from both strains, before or after activation by subcutaneous infection, was similar.
Insights
Mouse strain susceptibility to blastomycosis depends on the infection route. Pulmonary infection showed opposite resistance patterns compared to intraperitoneal infection, regardless of fungal strain virulence.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Pulmonary blastomycosis susceptibility varies between mouse strains C3H/HeJ (susceptible) and DBA/1J (resistant).
- Blastomyces dermatitidis is a fungus causing blastomycosis, a potentially severe infection.
Purpose of the Study:
- To investigate the influence of infection route on the differential susceptibility of C3H/HeJ and DBA/1J mice to Blastomyces dermatitidis.
- To compare the in vitro macrophage response of these strains to Blastomyces dermatitidis.
Main Methods:
- Infection of C3H/HeJ and DBA/1J mice via pulmonary, intraperitoneal, and subcutaneous routes using virulent and attenuated Blastomyces dermatitidis strains.
- In vitro assessment of Blastomyces dermatitidis replication inhibition by macrophages from both mouse strains, before and after activation.
Main Results:
- Pulmonary infection susceptibility followed the expected pattern (C3H/HeJ > DBA/1J).
- Intraperitoneal infection completely reversed the susceptibility pattern (DBA/1J > C3H/HeJ) for both fungal strains.
- Subcutaneous infection showed insignificant differences in susceptibility between the strains.
- Macrophage inhibition of Blastomyces dermatitidis replication in vitro was similar for both strains, irrespective of prior activation.
Conclusions:
- The route of Blastomyces dermatitidis infection critically determines the differential susceptibility of inbred mouse strains.
- Innate or activated macrophage function in vitro does not fully explain the observed in vivo resistance or susceptibility differences based on infection route.