Am. J. Respir. Crit. Care Med., Vol 149, No. 2, 02 1994, 500-509.
Development of pulmonary infection in mice inoculated with Blastomyces dermatitidis conidia
JE Williams, SA Moser, SH Turner and PG Standard
Department of Pathology, University of Wisconsin Medical School at Sinai Samaritan Medical Center, Milwaukee.
Intratracheal injection of Balb/cByJ mice with 10(4) Blastomyces
dermatitidis conida produces chronic pulmonary and disseminated
blastomycosis characterized by pyogranulomatous inflammation. To study the
evolution of the pulmonary infection, mice were killed at varying intervals
after inoculation, their lungs cultured and examined histologically.
Nodular intraalveolar infiltrates of macrophages (M phi) were seen on Day 1
with occasional admixed polymorphonuclear leukocytes (PMN). Phagocytized
yeast forms within M phi were evident by Day 5. By Day 28 pyogranulomas,
which developed first as central microabscesses associated with a
peripheral zone of M phi and giant cells containing internalized yeast,
were a prominent feature of the infection. Lymphocytic and plasmacytic
infiltrates, accumulating next to granulomas, formed the major peripheral
component of the granuloma by Day 35. Formation of pyogranulomas was
coincident with the host's failure to contain fungal growth measured by the
sharp rise in colony- forming units recovered from lungs. Antibody against
B. dermatitidis was first detected at Day 35 by enzyme immunoassay, but not
until Day 63 by double immunodiffusion. During the 4 wk after inoculation,
pulmonary lavage fluid contained > 90% M phi and < 3% PMN. On day 28,
PMN rose to 17%, reaching 40% on Day 42. These data contribute to our
knowledge of this model and help form the basis for investigations into the
roles of fungal pathogenic and host defense mechanisms in blastomycosis.