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Interactions of bacillus anthracis with the innate immune system during early infection
| Title: | Interactions of bacillus anthracis with the innate immune system during early infection |
| Author: | Premanandan, Christopher |
| Description: | Bacillus anthracis is a gram-positive, spore forming facultative anaerobic bacteria and is the etiologic agent for anthrax. Pulmonary anthrax is the form associated with the highest mortality in humans and is considered a significant threat due to its potential as a bioterrorist weapon. We examined the functionality and the expression of mRNA transcripts for anthrax toxin receptors in primary macrophages and several cell lines. We assessed receptor functionality by comparing the ability of macrophage cell lines and primary macrophages to translocate edema factor to the cytosol. We also examined the expression of TEM8 and CMG2 mRNA transcripts in human and mouse macrophages and mouse tissues by standard and real-time RT-PCR. Our results indicate that most cell lines and primary macrophages express functional anthrax toxin receptors and that CMG2 transcripts are preferentially expressed over TEM8 transcripts in primary macrophages. In order to determine if immunoglobulin and complement are involved in the phagocytosis of B. anthracis spores, we characterized the binding of human IgG and complement protein C3b to the surface of spores in nonimmune human serum. We showed that spores activate the classical complement pathway and that C3b, but not immunoglobulin, serves as an opsonin for spores resulting in enhanced phagocytosis by human macrophages. Thus, C3b opsonization of B. anthracis spores provides a mechanism for enhanced phagocytosis of spores by human macrophages. These findings led us to hypothesize that antibody against spores of other Bacillus species would be cross reactive with B. anthracis spores. We showed antibody and C3b deposition takes place when spores are incubated in antiserum against B. cereus and B. anthracis Sterne. In addition, we showed a complement and immunoglobulin dependent increase in spore phagocytosis by mouse macrophages in the presence of spore antiserum as compared to unvaccinated mouse serum or recombinant B. anthracis protective antigen antiserum. In conclusion, we show that functional anthrax toxin receptors, predominately CMG2, are present in primary mononuclear phagocytes, which provide target for intoxication and possible mechanism for escape during early infection. In addition, we show that complement opsonization plays a role in the interaction between B. anthracis spores and mononuclear phagocytes. |
| Permanent Link: |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1173290465
http://hdl.handle.net/2374.OX/4841 |
| Date: | 2007 |
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