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Mycobacterial Membrane Vesicles Administered Systemically in Mice Induce a Protective Immune Response to Surface Compartments of Mycobacterium Tuberculosis

Description

Pathogenic and nonpathogenic species of bacteria and fungi release membrane vesicles (MV), containing proteins, polysaccharides, and lipids, into the extracellular milieu. Previously, we demonstrated that several mycobacterial species, including bacillus Calmette-Guerin (BCG) and Mycobacterium tuberculosis, release MV containing lipids and proteins that subvert host immune response in a Toll-like receptor…

Pathogenic and nonpathogenic species of bacteria and fungi release membrane vesicles (MV), containing proteins, polysaccharides, and lipids, into the extracellular milieu. Previously, we demonstrated that several mycobacterial species, including bacillus Calmette-Guerin (BCG) and Mycobacterium tuberculosis, release MV containing lipids and proteins that subvert host immune response in a Toll-like receptor 2 (TLR2)-dependent manner (R. Prados-Rosales et al., J. Clin. Invest. 121:1471–1483, 2011, doi:10.1172/JCI44261). In this work, we analyzed the vaccine potential of MV in a mouse model and compared the effects of immunization with MV to those of standard BCG vaccination. Immunization with MV from BCG or M. tuberculosis elicited a mixed humoral and cellular response directed to both membrane and cell wall components, such as lipoproteins. However, only vaccination with M. tuberculosis MV was able to protect as well as live BCG immunization. M. tuberculosis MV boosted BCG vaccine efficacy. In summary, MV are highly immunogenic without adjuvants and elicit immune responses comparable to those achieved with BCG in protection against M. tuberculosis.
ContributorsPrados-Rosales, Rafael (Author) / Carreno, Leandro J. (Author) / Batista-Gonzalez, Ana (Author) / Baena, Andres (Author) / Venkataswamy, Manjunatha M. (Author) / Xu, Jiayong (Author) / Yu, Xiaobo (Author) / Wallstrom, Garrick (Author) / Magee, Mitch (Author) / LaBaer, Joshua (Author) / Achkar, Jacqueline M. (Author) / Jacobs, William R. (Author) / Chan, John (Author) / Porcelli, Steven A. (Author) / Casadevall, Arturo (Author) / Biodesign Institute (Contributor)
Created2014-09-30
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Forensic bitemark identification: weak foundations, exaggerated claims

Description
Several forensic sciences, especially of the pattern-matching kind, are increasingly seen to lack the scientific foundation needed to justify continuing admission as trial evidence. Indeed, several have been abolished in the recent past. A likely next candidate for elimination is bitemark identification. A number of DNA exonerations have occurred in…

Several forensic sciences, especially of the pattern-matching kind, are increasingly seen to lack the scientific foundation needed to justify continuing admission as trial evidence. Indeed, several have been abolished in the recent past. A likely next candidate for elimination is bitemark identification. A number of DNA exonerations have occurred in recent years for individuals convicted based on erroneous bitemark identifications. Intense scientific and legal scrutiny has resulted. An important National Academies review found little scientific support for the field. The Texas Forensic Science Commission recently recommended a moratorium on the admission of bitemark expert testimony. The California Supreme Court has a case before it that could start a national dismantling of forensic odontology. This article describes the (legal) basis for the rise of bitemark identification and the (scientific) basis for its impending fall. The article explains the general logic of forensic identification, the claims of bitemark identification, and reviews relevant empirical research on bitemark identification—highlighting both the lack of research and the lack of support provided by what research does exist. The rise and possible fall of bitemark identification evidence has broader implications—highlighting the weak scientific culture of forensic science and the law's difficulty in evaluating and responding to unreliable and unscientific evidence.
ContributorsSaks, Michael (Author) / Albright, Thomas (Author) / Bohan, Thomas L. (Author) / Bierer, Barbara E. (Author) / Bowers, C. Michael (Author) / Bush, Mary A. (Author) / Bush, Peter J. (Author) / Casadevall, Arturo (Author) / Cole, Simon A. (Author) / Denton, M. Bonner (Author) / Seidman Diamond, Shari (Author) / Dioso-Villa, Rachel (Author) / Epstein, Jules (Author) / Faigman, David (Author) / Faigman, Lisa (Author) / Fienberg, Stephen E. (Author) / Garrett, Brandon L. (Author) / Giannelli, Paul C. (Author) / Greely, Henry T. (Author) / Imwinkelried, Edward (Author) / Jamieson, Allan (Author) / Kafadar, Karen (Author) / Kassirer, Jerome P. (Author) / Koehler, Jonathan 'Jay' (Author) / Korn, David (Author) / Mnookin, Jennifer (Author) / Morrison, Alan B. (Author) / Murphy, Erin (Author) / Peerwani, Nizam (Author) / Peterson, Joseph L. (Author) / Risinger, D. Michael (Author) / Sensabaugh, George F. (Author) / Spiegelman, Clifford (Author) / Stern, Hal (Author) / Thompson, William C. (Author) / Wayman, James L. (Author) / Zabell, Sandy (Author) / Zumwalt, Ross E. (Author) / Sandra Day O'Connor College of Law (Contributor)
Created2016-11-23