Mechanisms of enhanced resistance of Mycobacterium bovis BCG-treated mice to ectromelia virus infection

Sakuma, Takashi; Suenaga, Tohru; Yoshida, Itsuro; Azuma, Mitsuo

doi:10.1128/iai.42.2.567-573.1983

Cited by 26 publications

(11 citation statements)

References 31 publications

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“…The first is that heterologous immunity can be demonstrated between mycobacteria and viruses. Earlier reports had indicated that BCG or M. tuberculosis infection provided resistance in mice to VV or ectromelia virus, but in those studies the virus challenge was early after immunization, when immune responses to the mycobacteria were likely ongoing (3,16,40,44,56). In this present report, mice were treated with antibiotics to clear residual mycobacteria to minimum levels, the immune system appeared at rest (Table 1; Fig.…”

Section: Discussionmentioning

confidence: 50%

“…This indicates that these BCG-immune hosts were in a resting immune state without an overt ongoing immune response. This distinguishes this study from previous reports on resistance of BCG-infected or M. tuberculosis-infected hosts to heterologous pathogens at 7 to 21 days after exposure to the mycobacteria (3,40,44,56).…”

Section: Status Of the Bcg-induced Resting Memory Statementioning

confidence: 63%

“…Vaccination against M. tuberculosis uses a closely related but less virulent strain of Mycobacterium bovis, referred to as bacillus Calmette-Guerin (BCG) (33). Several early reports indicated that a recent exposure of mice to BCG or to M. tuberculosis rendered them more resistant to infection to a variety of bacteria and to ectromelia virus (16,40,44), the mouse form of smallpox, and to VV (3,56), which is used for vaccination of humans against smallpox. An unspecified IFN was suggested to be involved in the protection against ectromelia virus (40,44).…”

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confidence: 99%

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CD4 T-Cell-Mediated Heterologous Immunity between Mycobacteria and Poxviruses

Mathurin¹,

Martens

Kornfeld

et al. 2009

J Virol

112

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The bacillus Calmette-Guerin (BCG) strain of Mycobacterium bovis is used in many parts of the world as a vaccine against Mycobacterium tuberculosis. Some epidemiological evidence has suggested that BCG immunization may have unpredicted effects on resistance to other pathogens. We show here in a mouse model that BCG immunization followed by antibiotic treatment to clear the host of the pathogen rendered three strains of mice partially resistant to infection with vaccinia virus (VV) but not to lymphocytic choriomeningitis virus (LCMV). VV-challenged BCG-immune mice developed a striking splenomegaly and elevated CD4 and CD8 T-cell responses by 6 days postinfection (p.i.). However, resistance to VV infection could be seen as early as 1 to 2 days p.i. and was lost after antibody depletion of CD4 T-cell populations. BCG-but not LCMV-immune memory phenotype CD4 T cells preferentially produced gamma interferon (IFN-␥) in vivo after VV challenge. In contrast, LCMV-immune CD8 T cells preferentially produced IFN-␥ in vivo in response to VV infection. In BCG-immune mice the resistance to VV infection and VV-induced CD4 T-cell IFN-␥ production were ablated by cyclosporine A, which inhibits signaling through the T-cell receptor. This study therefore demonstrates CD4 T-cell-mediated heterologous immunity between a bacterium and virus. Further, it poses the question of whether BCG immunization of humans alters resistance to unrelated pathogens.

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Section: Discussionmentioning

confidence: 50%

Section: Status Of the Bcg-induced Resting Memory Statementioning

confidence: 63%

mentioning

confidence: 99%

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CD4 T-Cell-Mediated Heterologous Immunity between Mycobacteria and Poxviruses

Mathurin¹,

Martens

Kornfeld

et al. 2009

J Virol

112

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“…Also, lower virus yields correlated with elevated interferon levels (fourto eightfold) in ascitic fluid and cultured peritoneal exudate cells or spleen cells (467). The importance of interferon in this system was further suggested by Sakuma et al (412), who showed that splenectomy of mice prior to treatment with BCG and infection with ectromelia virus (Ishibashi strain) resulted in a more severe infection and reduced levels of interferon in serum. Peritoneal exudate cells from mice treated 7 days earlier with another immunomodulator, Corynebacterium parvum, were not productively infected by ectromelia virus (Hampstead and Moscow strains), even though adsorption and penetration of the virus was unaffected (99).…”

Section: Interferonsmentioning

confidence: 90%

Poxvirus pathogenesis.

Buller

Palumbo

1991

Microbiological Reviews

293

163

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Marchal (285) and Downie (126) bodies, respectively. Because of the ambiguity associated with describing structures solely on the basis of their reaction with various histochemical stains, Kato et al. (253) carefully examined the virusspecific cytoplasmic structures of a large number of poxvirus species and, using a criterion based on morphologic observations, histochemical staining, and immunochemical reactivity, suggested that the acidophilic and basophilic inclusion bodies be referred to as A-and B-type inclusion bodies, respectively. Under the auspices of a Poxvirus Subcommittee created at the Sixth International Congress for Microbiology in 1953, Fenner and Burnet (161) wrote a review which summarized the characteristics of the poxvirus group. This article remains the basis for the subsequent classification of poxviruses. The poxvirus family is divided into two subfamilies: Entomopoxvirinae (poxviruses of the insects) and Chordopoxvirinae (poxviruses of the vertebrates); the latter group of viruses is the focus of this review (Table 1). The vertebrate poxviruses share a group-specific NP antigen (511) and are able, in a reciprocal fashion, to participate in nongenetic reactivation (160, 168). This is a process whereby an infectious poxvirus is able to reactivate a second, heatinactivated poxvirus, as indicated by the production of progeny virus. Poxviruses were further classified into genera by comparing cross-protection in animal studies, crossneutralization of infectivity in tissue culture, and crosshybridization of genomic DNA from virions. This latter criterion is now the method of choice for preliminary classification of poxvirus isolates. In general, members of the same genera have similar morphology and biological properties. Virion Morphology Poxviruses are the largest of all animal viruses and can be visualized by light microscopy, although the details of the

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“…Trained immunity refers to immunological memory within the innate immune system, leading to an augmented response to subsequent, often heterologous insults (13). Innate immune memory is induced in animals after vaccination with BCG (14,15) although the precise mechanisms via which this occurs are still being studied. Studies of TB contacts show that despite high levels of exposure, up to 30-50% of individuals do not become infected with M.tb, as evidenced by non-reactive tuberculin skin tests and negative IFN-γ release assay (IGRA) testing (16).…”

Section: Trained Immunitymentioning

confidence: 99%

Local Pulmonary Immunological Biomarkers in Tuberculosis

Morrison

McShane

2021

Front. Immunol.

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Regardless of the eventual site of disease, the point of entry for Mycobacterium tuberculosis (M.tb) is via the respiratory tract and tuberculosis (TB) remains primarily a disease of the lungs. Immunological biomarkers detected from the respiratory compartment may be of particular interest in understanding the complex immune response to M.tb infection and may more accurately reflect disease activity than those seen in peripheral samples. Studies in humans and a variety of animal models have shown that biomarkers detected in response to mycobacterial challenge are highly localized, with signals seen in respiratory samples that are absent from the peripheral blood. Increased understanding of the role of pulmonary specific biomarkers may prove particularly valuable in the field of TB vaccines. Here, development of vaccine candidates is hampered by the lack of defined correlates of protection (COPs). Assessing vaccine immunogenicity in humans has primarily focussed on detecting these potential markers of protection in peripheral blood. However, further understanding of the importance of local pulmonary immune responses suggests alternative approaches may be necessary. For example, non-circulating tissue resident memory T cells (TRM) play a key role in host mycobacterial defenses and detecting their associated biomarkers can only be achieved by interrogating respiratory samples such as bronchoalveolar lavage fluid or tissue biopsies. Here, we review what is known about pulmonary specific immunological biomarkers and discuss potential applications and further research needs.

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Mechanisms of enhanced resistance of Mycobacterium bovis BCG-treated mice to ectromelia virus infection

Cited by 26 publications

References 31 publications

CD4 T-Cell-Mediated Heterologous Immunity between Mycobacteria and Poxviruses

CD4 T-Cell-Mediated Heterologous Immunity between Mycobacteria and Poxviruses

Poxvirus pathogenesis.

Local Pulmonary Immunological Biomarkers in Tuberculosis

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