The lung is the portal of entry for many important fungal pathogens including Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. Mechanisms of host defense against fungal pathogens are poorly understood. In particular we know very little about the role of antibody-mediated immune responses in either the protection against or the pathogenesis of infection. The question of how antibody participates in lung defense is important for both the fundamental understanding of host defense mechanisms and the practical goals of vaccine design. Antibody responses to fungal antigens could, in theory, be protective, deleterious, or irrelevant to the host. Recently, this laboratory has shown that antibody administration protects against pulmonary C. neoformans infection in mice. Studies of lung tissue response in antibody-treated and control mice suggests that antibody functions enhancing cellular immunity in the lung. This application proposes to explore mechanisms by which antibody and cellular immunity collaborate and cooperate against microorganisms in the lung.
Three specific aims are proposed: 1. To determine the role of Th1- and Th2-associated cytokines in antibody-mediated protection against pulmonary C. neoformans infection; 2. To determine the relationship between antibody-mediated protective effects in the lung and nitric oxide production; and 3. To determine the effect of polysaccharide-protein conjugate vaccination on pulmonary defenses against C. neoformans in the context of cytokine- and nitric oxide-related mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059842-02
Application #
2771663
Study Section
Special Emphasis Panel (ZHL1-CSR-H (S1))
Project Start
1997-09-30
Project End
2002-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
Vij, Raghav; Cordero, Radames J B; Casadevall, Arturo (2018) The Buoyancy of Cryptococcus neoformans Is Affected by Capsule Size. mSphere 3:
Rizzo, Juliana; Colombo, Ana C; Zamith-Miranda, Daniel et al. (2018) The putative flippase Apt1 is required for intracellular membrane architecture and biosynthesis of polysaccharide and lipids in Cryptococcus neoformans. Biochim Biophys Acta Mol Cell Res 1865:532-541
Casadevall, Arturo (2018) Antibody-based vaccine strategies against intracellular pathogens. Curr Opin Immunol 53:74-80
Jung, Eric H; Meyers, David J; Bosch, Jürgen et al. (2018) Novel Antifungal Compounds Discovered in Medicines for Malaria Venture's Malaria Box. mSphere 3:
Fu, Man Shun; Coelho, Carolina; De Leon-Rodriguez, Carlos M et al. (2018) Cryptococcus neoformans urease affects the outcome of intracellular pathogenesis by modulating phagolysosomal pH. PLoS Pathog 14:e1007144
Goldman, David L; Nieves, Edward; Nakouzi, Antonio et al. (2018) Serum-Mediated Cleavage of Bacillus anthracis Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase. mSphere 3:
Casadevall, Arturo; Pirofski, Liise-Anne (2018) What Is a Host? Attributes of Individual Susceptibility. Infect Immun 86:
Fu, Man Shun; Casadevall, Arturo (2018) Divalent Metal Cations Potentiate the Predatory Capacity of Amoeba for Cryptococcus neoformans. Appl Environ Microbiol 84:
De Leon-Rodriguez, Carlos M; Rossi, Diego C P; Fu, Man Shun et al. (2018) The Outcome of the Cryptococcus neoformans-Macrophage Interaction Depends on Phagolysosomal Membrane Integrity. J Immunol 201:583-603
Walker, Louise; Sood, Prashant; Lenardon, Megan D et al. (2018) The Viscoelastic Properties of the Fungal Cell Wall Allow Traffic of AmBisome as Intact Liposome Vesicles. MBio 9:

Showing the most recent 10 out of 290 publications