CONSERVED NATURAL lgM ANTIBODIES MEDIATE INNATE AND ADAPTIVE IMMUNE RESPONSES AND HOST DEFENSE AGAINST OPPORTUNISTIC FUNGI
Document Type
Presentation
Start Date
22-10-2010 3:00 PM
End Date
22-10-2010 4:30 PM
Description
Pneumocystis (PC) pneumonia is a common opportunistic fungal infection in severely immunocompromised individuals, such as those with AIDS, cancer, and organ transplantations. (1,3) 13-D-glucan and chitin are common components of the fungal cell wall and major components of PC cysts, and PC challenge in mice leads to the induction of specific antibody responses against these carbohydrates. We have identified and sought to characterize natural lgM antibodies to j3-glucan and chitin/chitosan. These antibodies, primarily produced by B cells resident in the spleen, are present in the absence of microbial stimulation and conserved across multiple vertebrate species. Natural anti-carbohydrate lgM was also detected in rhesus and human cord blood. In mice, naive serum containing natural antibodies impairs the growth of PC organisms in the lungs at intermediate stages of infection. Mice unable to secrete lgM, slgM(-/-), manifest deficiencies in pathogen clearance at intermediate stages of infection, diminished trafficking of fungal cell wall carbohydrate antigen by CD11 c+ cells to draining lymph nodes, and impaired production of Th2 and Th17 cytokines in lymph nodes after PC challenge. Additionally, slgM(-/-) mice exhibit altered anti-PC adaptive antibody responses, with diminished Th2associated lgG1 response and enhanced Th1-associated lgG2a response. Thus, secreted lgM, of which a significant component is natural antibody, influences PC antigen presentation at the earliest stages of infection, enhancing host defense and biasing the host towards Th2 adaptive responses. Collectively, these studies demonstrate the importance of conserved fungal cell wall carbohydrate antigens and primitive antibody isotypes in host defense responses against PC.
Recommended Citation
Ricks, David; Rapaka, R. R.; Alcorn, J. F.; and Khader, S. A., "CONSERVED NATURAL lgM ANTIBODIES MEDIATE INNATE AND ADAPTIVE IMMUNE RESPONSES AND HOST DEFENSE AGAINST OPPORTUNISTIC FUNGI" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 19.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster2/19
CONSERVED NATURAL lgM ANTIBODIES MEDIATE INNATE AND ADAPTIVE IMMUNE RESPONSES AND HOST DEFENSE AGAINST OPPORTUNISTIC FUNGI
Pneumocystis (PC) pneumonia is a common opportunistic fungal infection in severely immunocompromised individuals, such as those with AIDS, cancer, and organ transplantations. (1,3) 13-D-glucan and chitin are common components of the fungal cell wall and major components of PC cysts, and PC challenge in mice leads to the induction of specific antibody responses against these carbohydrates. We have identified and sought to characterize natural lgM antibodies to j3-glucan and chitin/chitosan. These antibodies, primarily produced by B cells resident in the spleen, are present in the absence of microbial stimulation and conserved across multiple vertebrate species. Natural anti-carbohydrate lgM was also detected in rhesus and human cord blood. In mice, naive serum containing natural antibodies impairs the growth of PC organisms in the lungs at intermediate stages of infection. Mice unable to secrete lgM, slgM(-/-), manifest deficiencies in pathogen clearance at intermediate stages of infection, diminished trafficking of fungal cell wall carbohydrate antigen by CD11 c+ cells to draining lymph nodes, and impaired production of Th2 and Th17 cytokines in lymph nodes after PC challenge. Additionally, slgM(-/-) mice exhibit altered anti-PC adaptive antibody responses, with diminished Th2associated lgG1 response and enhanced Th1-associated lgG2a response. Thus, secreted lgM, of which a significant component is natural antibody, influences PC antigen presentation at the earliest stages of infection, enhancing host defense and biasing the host towards Th2 adaptive responses. Collectively, these studies demonstrate the importance of conserved fungal cell wall carbohydrate antigens and primitive antibody isotypes in host defense responses against PC.
Comments
See abstract book page 63