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Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 14, 2011
Anti-glucuronoxylomannan IgG1 specific antibodies production in Cryptococcus neoformans resistant mice
Claudia Parra1, John Mario González, Elizabeth Castañeda
1Grupo de Inmunobiología, Departamento de Microbiología, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.
Background:
Cryptococcus neoformans is a widely disseminated fungus shown to be responsible for infections in individuals with impaired cell mediated immunity, such as patients with human immunodeficiency virus (HIV). Cryptococcus neoformans has a polysaccharide capsule composed of glucuronoxylomannan (GXM), which acts as a major virulence factor and is considered to be a thymus independent type-2 antigen (TI-2).
Objective:
In the current study, the production kinetics were evaluated for IgG subclasses specific for GXM, and assessed with the cross reactive antibodies to Streptococcus pneumoniae polysaccharide. In addition, spleen B cell subpopulations were quantified in murine models of cryptococcosis with different susceptibilities to the infection.
Materials And Methods:
Antibodies were detected by ELISA at different time intervals after C. neoformans infection in moderately resistant (Balb/c), highly resistant (CBA/j) and susceptible (C57BL/6) mouse strains. B cells subpopulations were determined by flow cytometry analysis.
Results:
Early production of IgG1, described as protector antibodies, coincided with a decrease of the number of C. neoformans colony forming units in the lungs. Polysaccharide cross-reactive antibodies were detected in each of the three mouse strains. Antibody titers were highest in the susceptible strain (C57BL/6), a strain which also showed the highest proportion of splenic CD5+ B lymphocytes. In contrast, CBA/J mice showed the highest levels of CD43+ B.
Conclusions:
These findings suggest that IgG1 antibodies specific for GXM, are implicated in host protection against C. neoformans infection and may be regulated by CD43+ cells. They also suggest that cross reactivity antibodies are not important in the protection against C. neoformans infection.
Insights
Host protection against Cryptococcus neoformans infection involves IgG1 antibodies specific for glucuronoxylomannan (GXM). These protective antibodies may be regulated by CD43+ cells, while cross-reactive antibodies offer no significant protection.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Cryptococcus neoformans is a significant fungal pathogen, particularly in immunocompromised individuals (e.g., HIV patients).
- The glucuronoxylomannan (GXM) capsule of C. neoformans is a key virulence factor and a thymus-independent type-2 antigen (TI-2).
Purpose of the Study:
- To investigate the production kinetics of IgG subclasses specific for GXM.
- To assess cross-reactivity of these antibodies with Streptococcus pneumoniae polysaccharide.
- To quantify spleen B cell subpopulations in mice with varying susceptibility to cryptococcosis.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in different mouse strains (Balb/c, CBA/j, C57BL/6) post-infection.
- Flow cytometry analysis was employed to determine B cell subpopulations.
Main Results:
- Early production of protective IgG1 antibodies correlated with reduced C. neoformans lung burden.
- Polysaccharide cross-reactive antibodies were present in all strains, with highest titers in susceptible C57BL/6 mice.
- Susceptible C57BL/6 mice had a higher proportion of splenic CD5+ B cells, while resistant CBA/J mice had higher CD43+ B cell levels.
Conclusions:
- IgG1 antibodies targeting GXM are crucial for host defense against C. neoformans, potentially regulated by CD43+ cells.
- Antibodies cross-reactive with Streptococcus pneumoniae polysaccharide do not appear to contribute to protection against C. neoformans.
