BCG: A modifier of immune responses to parasites

Frommel, D.; Lagrange, Philippe

doi:10.1016/0169-4758(89)90143-9

Cited by 22 publications

(9 citation statements)

References 19 publications

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“…A positive DTH response towards leishmanial antigens is an indication of cell-mediated immunity, and there are reports of an association between the DTH response and protection in the L. major system (11,19,41). Development of DTH in UR6-immunized infected mice, in contrast with its suppression in nonimmunized controls, coincided with control or progression of disease in the respective groups.…”

Section: Discussionmentioning

confidence: 86%

Use of an Attenuated Leishmanial Parasite as an Immunoprophylactic and Immunotherapeutic Agent against Murine Visceral Leishmaniasis

Mukhopadhyay

Bhattacharyya

Majhi

et al. 2000

Clin Diagn Lab Immunol

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The ability of the leishmanial parasite UR6 to act as an immunoprophylactic and immunotherapeutic agent against Leishmania donovani infection in BALB/c mice was investigated. Unlike the virulent L. donovani AG83 (MOHOM/IN/1983/AG83), UR6 given through intracardiac route failed to induce visceral infection, but when it was injected subcutaneously, UR6 induced a short-lived and localized self-healing skin lesion. Priming of peritoneal macrophages with UR6 in vitro induced superoxide (O 2 ؊ ) generation, whereas similar experiments with virulent AG83 inhibited O 2 ؊ generation. It was observed that priming of mice with either live or sonicated UR6 in the absence of any adjuvant provided strong protection against subsequent virulent challenge. Further, UR6-primed infected mice not only displayed a strong antileishmanial delayed-type hypersensitivity (DTH) response but also showed an elevated level of the serum antileishmanial immunoglobulin G2a (IgG2a) isotype, whereas infected mice failed to mount any antileishmanial DTH response and showed an elevated level of IgG1. This indicates that UR6 priming and subsequent L. donovani infection allowed the expansion of Th1 cells. Our studies indicate that UR6 has potential to be used as an immunoprophylactic and immunotherapeutic agent against experimental visceral leishmaniasis.

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Section: Discussionmentioning

confidence: 86%

Use of an Attenuated Leishmanial Parasite as an Immunoprophylactic and Immunotherapeutic Agent against Murine Visceral Leishmaniasis

Mukhopadhyay

Bhattacharyya

Majhi

et al. 2000

Clin Diagn Lab Immunol

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“…As the mycobacteria are known to be able to stimulate some compartments of the immune system nonspecifically [26], it was decided to evaluate the effect of priming with live BCG on immunization with a conjugate made of a T cell epitope, bearing no relation to the mycobacteria, coupled to (NA")m peptide. A synthetic peptide, referred to as Pyl, from the CS protein of the murine malaria parasite l?…”

Section: Mycobacterial Carrier Molecules Are Required For the Inductimentioning

confidence: 99%

Mycobacterial heat‐shock proteins as carrier molecules

et al. 1991

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We have previously shown that the priming of mice with live Mycobacterium tuberculosis var. bovis (Bacillus Calmette-Guérin, BCG) and immunization with the repetitive malaria synthetic peptide (NANP)40 conjugated to purified protein derivative (PPD), led to the induction of high and long-lasting titers of anti-peptide IgG antibodies, overcoming the requirement of adjuvants and the genetic restriction of the antibody response to the peptide (Lussow et al., Proc. Natl. Acad. Sci. USA 1990. 87:2960). This initial work led us to the following observations. BCG had to be live for priming to lead to the induction of anti-peptide antibodies. Surprisingly, priming with other living microorganisms which chronically infect the macrophage (e.g. Salmonella typhimurium and Leishmania major) also induced anti-peptide antibodies in mice immunized with PPD-(NANP)40 conjugate. It was, thus, hypothesized that molecules expressed during active infection and also known to be highly conserved between species, namely the heat-shock proteins (hsp), could mediate the T cell sensitization required for the production of anti-peptide antibodies. In fact, when the PPD protion of the conjugate was replaced by a highly purified recombinant protein corresponding to the 65-kDa (GroEL-type) hsp of M. bovis, this resulted in the production of anti-(NANP) IgG antibodies in BCG-primed mice, irrespective of the major histocompatibility complex-controlled responsiveness to the (NANP) sequence itself. Further, similar induction of anti-peptide antibody response was also obtained with a recombinant 70-kDa (DnaK-type) hsp of M. tuberculosis, but not with a small molecular mass (18 kDa) of M. leprae. Finally, an adjuvant-free carrier effect for anti-peptide IgG antibody production in BCG-primed mice, was also exerted by the GroEL hsp of Escherichia coli. This finding that hsp can act as carrier molecules without requiring conventional adjuvants is of potential importance in the development of vaccine strategies.

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“…The ability of BCG to trigger IL-12 production by macrophages (Matsumoto et al 1997), which is enhanced in the presence of natural killer cells, will bias this towards a Th1 response. In humans (Convit et al , 1989 and in mice (Frommel & Lagrange 1989), BCG alone administered at a site remote to the lesions is capable of mediating protection or cure. This suggests that there must be stimulation of T cells to BCG antigen epitopes cross-reactive with leishmanial antigens presented at the site of infection.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients

Cabrera

Blackwell

Castes

et al. 2000

Parasite Immunology

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Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)-gamma and interleukin (IL)-5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL-5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN-gamma responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN-gamma responses to BCG. Treatment enhanced the IFN-gamma response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN-gamma responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL-5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL-5 levels. There were no significant changes in serum IL-5 with treatment. Overall results show enhanced antigen-specific IFN-gamma responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN-gamma.

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BCG: A modifier of immune responses to parasites

Cited by 22 publications

References 19 publications

Use of an Attenuated Leishmanial Parasite as an Immunoprophylactic and Immunotherapeutic Agent against Murine Visceral Leishmaniasis

Use of an Attenuated Leishmanial Parasite as an Immunoprophylactic and Immunotherapeutic Agent against Murine Visceral Leishmaniasis

Mycobacterial heat‐shock proteins as carrier molecules

Immunotherapy with live BCG plus heat killed Leishmania induces a T helper 1‐like response in American cutaneous leishmaniasis patients

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