title: The absence of serum IgM enhances the susceptibility of mice to pulmonary challenge with Cryptococcus neoformans.
abstract: The importance of T cell-mediated immunity for resistance to the disease (cryptococcal disease) caused by Cryptococcus neoformans is incontrovertible, but whether Ab immunity also contributes to resistance remains uncertain. To investigate the role of IgM in resistance to C. neoformans, we compared the survival, fungal burden, lung and brain inflammatory responses, and lung phagocytic response of sIgM(-/-) mice, which lack secreted IgM, to that of IgM sufficient C57BL6x129Sv (heretofore, control) mice at different times after intranasal infection with C. neoformans (24067). sIgM(-/-) mice had higher mortality and higher blood and brain CFUs 28 d postinfection, but lung CFUs were comparable. Lungs of control mice manifested exuberant histiocytic inflammation with visible C. neoformans, findings that were not observed in sIgM(-/-) mice, whereas in brain sections, sIgM(-/-) mice had marked inflammation with visible C. neoformans that was not observed in control mice. Cytokine responses were significant for higher levels of lung IL-1beta and IL-12 24 h postinfection in control mice and higher levels of lung and brain IL-17 28 d postinfection in sIgM(-/-) mice. Alveolar macrophage phagocytosis was significantly higher for control than for sIgM(-/-) mice 24 h postinfection; however, phagocytic indices of sIgM(-/-) mice increased after reconstitution of sIgM(-/-) mice with polyclonal IgM. These data establish a previously unrecognized role for IgM in resistance to intranasal infection with C. neoformans in mice and suggest that the mechanism by which it mediates a host benefit is by augmenting Th1 polarization, macrophage recruitment and phagocytosis of C. neoformans.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine of the Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Krishanthi S
authors.initials: KS
authors.lastname: Subramaniam
authors.forename: Kausik
authors.initials: K
authors.lastname: Datta
authors.forename: Eric
authors.initials: E
authors.lastname: Quintero
authors.forename: Catherine
authors.initials: C
authors.lastname: Manix
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Marks
authors.forename: Liise-Anne
authors.initials: LA
authors.lastname: Pirofski
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood* / Q000235:genetics; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D003455:Cryptococcus neoformans / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D007075:Immunoglobulin M / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008172:Lung Diseases, Fungal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007075:Immunoglobulin M
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