RESUMO
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies. Animals studied included four genetically distinct groups of macaques within cynomolgus and rhesus species that differ in their susceptibility to Mtb infection. We demonstrate significant differences in ex vivo iNKT frequency between groups, which trends towards an association with susceptibility to Mtb, but no significant difference in overall iNKT proliferative responses. Susceptible animals exhibited a skewed CD4+/CD8+ iNKT subset ratio in comparison to more Mtb-resistant groups. Correlation of iNKT subsets post BCG vaccination with clinical disease manifestations following Mtb challenge in the Chinese cynomolgus and Indian rhesus macaques identified a consistent trend linking increased CD8+ iNKTs with favourable disease outcome. Finally, a similar iNKT profile was conferred by BCG vaccination in rhesus macaques. Our study provides the first detailed characterisation of iNKT cells in macaque tuberculosis infection, suggesting that iNKT repertoire differences may impact on disease outcome, which warrants further investigation.
Assuntos
Mycobacterium tuberculosis/imunologia , Células T Matadoras Naturais/imunologia , Tuberculose Pulmonar/imunologia , Animais , Antígenos CD1d/sangue , Antígenos CD1d/imunologia , Vacina BCG/administração & dosagem , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/microbiologia , Proliferação de Células , Células Cultivadas , Citocinas/sangue , Citocinas/imunologia , Modelos Animais de Doenças , Galactosilceramidas/farmacologia , Predisposição Genética para Doença , Interações Hospedeiro-Patógeno , Pulmão/imunologia , Pulmão/microbiologia , Ativação Linfocitária , Macaca fascicularis , Macaca mulatta , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/microbiologia , Fenótipo , Especificidade da Espécie , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/prevenção & controle , VacinaçãoRESUMO
BACKGROUND: Research antibodies are used by thousands of scientists working in diverse disciplines, but it is common to hear concerns about antibody quality. This means that researchers need to carefully choose the antibodies they use to avoid wasting time and money. A well accepted way of selecting a research antibody is to identify one which has been used previously, where the associated data has been peer-reviewed and the results published. DESCRIPTION: CiteAb is a searchable database which ranks antibodies by the number of times they have been cited. This allows researchers to easily find antibodies that have been used in peer-reviewed publications and the accompanying citations are listed, so users can check the data contained within the publications. This makes CiteAb a useful resource for identifying antibodies for experiments and also for finding information to demonstrate antibody validation. The database currently contains 1,400,000 antibodies which are from 90 suppliers, including 87 commercial companies and 3 academic resources. Associated with these antibodies are 140,000 publications which provide 306,000 antibody citations. In addition to searching, users can also browse through the antibodies and add their own publications to the CiteAb database. CONCLUSIONS: CiteAb provides a new way for researchers to find research antibodies that have been used successfully in peer-reviewed publications. It aims to assist these researchers and will hopefully help promote progress in many areas of life science research.
Assuntos
Anticorpos/análise , Bases de Dados de Proteínas , Ferramenta de Busca , Interface Usuário-Computador , Animais , Humanos , InternetRESUMO
Research antibodies are used in a wide range of bioscience disciplines, yet it is common to hear dissatisfaction amongst researchers with respect to their quality. Although blame is often attributed to the manufacturers, scientists are not doing all they can to help themselves. One example of this is in the reporting of research antibody use. Publications routinely lack key details, including the host species, code number and even the company who supplied the antibody. Authors also fail to demonstrate that validation of the antibodies has taken place. These omissions make it harder for reviewers to establish the likely reliability of the results and for researchers to reproduce the experiments. The scale of this problem, combined with high profile concerns about experimental reproducibility, has caused the Nature Publishing Group to include a section on antibody information in their recent Reporting Checklist for Life Science Articles. In this commentary we consider the issue of reporting research antibody use and ask what details authors should be including in their publications to improve experimental reproducibility.