Maturity as a critical determinant of resistance to fungal infections: studies in murine blastomycosis

Abstract

Marked resistance of 9-week-old mice as compared to that of 5-week-old mice was demonstrated after pulmonary challenge with three strains of Blastomyces dermatitidis of various virulences. Quantitative studies with graded doses of the strain that was intermediate in virulence indicated that the difference in resistance between the two age groups was 1,000-fold. Acquisition of resistance appeared to be gradual between the ages of 5 and 9 weeks. Maturational differences among individual mice appeared to be most crucial at 5 weeks of age. With two fungal strains, susceptibility of the younger mice was also demonstrated after intraperitoneal challenge; with one of these strains, the differences between the two groups of mice were much smaller, suggesting that maturation of defenses in the peritoneal cavity may develop faster. Studies with serial sacrifice of different groups of mice given pulmonary challenges (of comparable amounts) indicated that the differences are not due to the amount of challenge reaching the lungs or its clearance. The infection-limiting effect in the lungs of older mice occurred within 4 days after challenge. These differences in resistance over this narrow age interval appear to be unique; resistance appears to occur later than resistance to other infectious agents and at a time when most murine immune functions have matured. This model and these observations provide an opportunity for further studies of the mechanism of resistance and are relevant to clinical observations of susceptibility of infants and children to deep mycoses.