In:
Infection and Immunity, American Society for Microbiology, Vol. 69, No. 3 ( 2001-03), p. 1433-1439
Abstract:
Vaccination of mice with Mycobacterium vaccae or M. smegmatis induces some protection against M. tuberculosis challenge. The 19-kDa lipoprotein of M. tuberculosis , expressed in M. vaccae or M. smegmatis ( M. smeg 19kDa), abrogates this protective immunity. To investigate the mechanism of this suppression of immunity, human monocyte-derived macrophages (MDM) were infected with M. smeg 19kDa. Infection resulted in reduced production of tumor necrosis factor alpha (TNF-α) ( P 〈 0.01), interleukin-12 (IL-12) ( P 〈 0.05), IL-6 ( P 〈 0.05), and IL-10 ( P 〈 0.05), compared to infection with M. smegmatis vector ( M. smeg V). Infection with M. smeg 19kDa and with M. smeg V had no differential effect on expression of costimulatory molecules on MDM, nor did it affect the proliferation of presensitized T cells cocultured with infected MDM. When MDM were infected with M. smegmatis expressing mutated forms of the 19-kDa lipoprotein, including non-O-glycosylated ( M. smeg 19NOG), nonsecreted ( M. smeg 19NS), and nonacylated ( M. smeg 19NA) variants, the reduced production of TNF-α or IL-12 was not observed. When the purified 19-kDa lipoprotein was added directly to cultures of infected monocytes, there was little effect on either induction of cytokine production or its inhibition. Thus, the immunosuppressive effect is dependent on glycosylated and acylated 19-kDa lipoprotein present in the phagosome containing the mycobacterium. These results suggest that the diminished protection against challenge with M. tuberculosis seen in mice vaccinated with M. smegmatis expressing the 19-kDa lipoprotein is the result of reduced TNF-α and IL-12 production, possibly leading to reduced induction of T-cell activation.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.69.3.1433-1439.2001
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2001
detail.hit.zdb_id:
1483247-1
Permalink