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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 317-323 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 190 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2013 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Immunology
Cite this
Antibody binding to Cryptococcus neoformans impairs budding by altering capsular mechanical properties. / Cordero-Gonzalez, Radames; Pontes, Bruno; Frases, Susana; Nakouzi, Antonio S.; Nimrichter, Leonardo; Rodrigues, Marcio L.; Viana, Nathan B.; Casadevall, Arturo.
In: Journal of Immunology, Vol. 190, No. 1, 01.01.2013, p. 317-323.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antibody binding to Cryptococcus neoformans impairs budding by altering capsular mechanical properties
AU - Cordero-Gonzalez, Radames
AU - Pontes, Bruno
AU - Frases, Susana
AU - Nakouzi, Antonio S.
AU - Nimrichter, Leonardo
AU - Rodrigues, Marcio L.
AU - Viana, Nathan B.
AU - Casadevall, Arturo
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84871840392&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871840392&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1202324
DO - 10.4049/jimmunol.1202324
M3 - Article
VL - 190
SP - 317
EP - 323
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 1
ER -