Abstract
Abs to microbial capsules are critical for host defense against encapsulated pathogens, but very little is known about the effects of Ab binding on the capsule, apart from producing qualitative capsular reactions (“quellung” effects). A problem in studying Ab–capsule interactions is the lack of experimental methodology, given that capsules are fragile, highly hydrated structures. In this study, we pioneered the use of optical tweezers microscopy to study Ab–capsule interactions. Binding of protective mAbs to the capsule of the fungal pathogen Cryptococcus neoformans impaired yeast budding by trapping newly emerging buds inside the parental capsule. This effect is due to profound mAb-mediated changes in capsular mechanical properties, demonstrated by a concentration-dependent increase in capsule stiffness. This increase involved mAb-mediated cross-linking of capsular polysaccharide molecules. These results provide new insights into Ab-mediated immunity, while suggesting a new nonclassical mechanism of Ab function, which may apply to other encapsulated pathogens. Our findings add to the growing body of evidence that Abs have direct antimicrobial functions independent of other components of the immune system.
Footnotes
This work was supported by National Institutes of Health Grants AI033774, HL059842, and AI033142 to A.C. and R.J.B.C. R.J.B.C. was also supported in part by the Training Program in Cellular and Molecular Biology and Genetics Grant T32 GM007491. The Casadevall laboratory is part of and participates in the Center for AIDS Research at the Albert Einstein College of Medicine and Montefiore Medical Center, funded by the National Institutes of Health (AI51519). B.P. and N.B.V. received grants from Conselho Nacional de Desenvolvimento Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and Instituto Nacional de Ciência e Tecnologia de Fluidos Complexos. S.F. received grants from Conselho Nacional de Desenvolvimento Tecnológico. M.L.R. and L.N. received grants from Conselho Nacional de Desenvolvimento Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Financiadora de Estudos e Projetos.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- DLS
- dynamic light scattering
- GXM
- glucuronoxylomannan
- PS
- polysaccharide.
- Received August 20, 2012.
- Accepted November 1, 2012.
- Copyright © 2012 by The American Association of Immunologists, Inc.
This article is distributed under The American Association of Immunologists, Inc., Reuse Terms and Conditions for Author Choice articles.
In this issue
