CBA/J mice generate protective immunity to soluble Ag85 but fail to respond efficiently to Ag85 during natural Mycobacterium tuberculosis infection

CBA/J mice generate protective immunity to soluble Ag85 but fail to respond efficiently to Ag85 during natural Mycobacterium tuberculosis infection
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DOI:
10.1002/eji.201142054
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发表时间:
2012-04-01
影响因子:
5.4
通讯作者:
Turner, Joanne
Turner, Joanne
中科院分区:
医学3区
文献类型:
--
作者:
Beamer, Gillian L.;Cyktor, Joshua;Turner, Joanne

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In CBA/J mice, susceptibility to Mycobacterium tuberculosis (M.tb) is associated with low interferon-gamma (IFN-?) responses to antigens (Antigen 85 (Ag85) and early secreted antigenic target-6 (ESAT-6)) that have been defined as immunodominant. Here, we asked whether the failure of CBA/J mice to recognize Ag85 is a consequence of M.tb infection or whether CBA/J mice have a general defect in generating specific T-cell responses to this protein antigen. We compared CBA/J mice during primary M.tb infection, Ag85 vaccination followed by M.tb challenge, or M.tb memory immune mice for their capacity to generate Ag85-specific IFN-? responses and to control M.tb infection. CBA/J mice did not respond efficiently to Ag85 in the context of natural infection or re-infection. In contrast, CBA/J mice could generate Ag85-specific IFN-? responses and protective immunity when this antigen was delivered as a soluble protein. Our data indicate that although M.tb infection of CBA/J mice does not drive an Ag85 response, these mice can fully and protectively respond to Ag85 if it is delivered as a vaccine. The data from this experimental model suggest that the Ag85-containing vaccines in clinical trials should protect M.tb susceptible humans.