Vaccinated Mice Remain More Susceptible to Mycobacterium tuberculosis Infection Initiated via the Respiratory Route than via the Intravenous Route

North, Robert J.; LaCourse, Ronald; Ryan, Lynn

doi:10.1128/.67.4.2010-2012.1999

Cited by 9 publications

(7 citation statements)

References 4 publications

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“…It has been shown by others that mycobacterial delivery directly to the lung induces a more severe disease compared to that induced by intravenous challenge, and that only 1% of mycobacteria delivered i.v. are deposited in the lung [8,45]. This corresponds well with our data.…”

Section: Discussionsupporting

confidence: 92%

Lung cell responses toM. tuberculosisin genetically susceptible and resistant mice following intratracheal challenge

Eruslanov

Majorov

Orlova

et al. 2003

Clinical and Experimental Immunology

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SUMMARYOne approach to study the role of distinct cellular mechanisms in susceptibility/resistance to tuberculosis (TB) is to compare parameters of response to infection in the lungs of mouse strains exhibiting genetically determined differences in TB susceptibility/severity. Interstrain differences in antimycobacterial macrophage reactions, T cell responses & inflammation in the lungs of TB-susceptible I/St, TBresistant A/Sn and (I/St ¥ A/Sn)F1 mice were analysed following intratracheal inoculation of 10 3 CFUs of M. tuberculosis H37Rv. The antimycobacterial responses in the lungs of susceptible I/St mice were characterized by: (i) increased inflammatory infiltration by all major immune cell subsets; (ii) decreased type 1 cytokine production; (iii) impaired antimycobacterial activity of lung macrophages; (iv) unusually high proliferation of lung T lymphocytes. Differences in several parameters of anti-TB immunity between susceptible and resistant mice corresponded well to the polygenic pattern of TB control previously established in this mouse model. Importantly, lung macrophages isolated from noninfected mice were unable to respond to IFN-g by increasing their mycobactericidal function, but between weeks 3 and 5 of the infection this capacity developed in all mice. However, by this time point susceptible but not resistant mice demonstrated a pronounced decrease in IFN-g production by lung cells. This chain of events may explain the inability of I/St mice to control both early and chronic TB infection.

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Section: Discussionsupporting

confidence: 92%

Lung cell responses toM. tuberculosisin genetically susceptible and resistant mice following intratracheal challenge

Eruslanov

Majorov

Orlova

et al. 2003

Clinical and Experimental Immunology

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“…Four weeks after the challenge, there were significantly fewer H37Rv bacteria in the lungs and spleens of mice rectally immunized as newborns or as adults than in those of age‐matched nonimmunized control mice. As found by others after intravenous challenge with H37Rv [18] the number of bacteria found in control spleen was 10‐fold higher than in the lungs. Mice rectally immunized as newborns developed more potent immunity than those immunized subcutaneously, as shown by the number of bacteria found in the lungs (Fig.…”

Section: Resultssupporting

confidence: 73%

Development of Mixed Th1/Th2 Type Immune Response and Protection Against Mycobacterium tuberculosis After Rectal or Subcutaneous Immunization of Newborn and Adult Mice with Mycobacterium bovis BCG

et al. 2002

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Cell-mediated immunity plays a key role in containing the growth of Mycobacterium tuberculosis in the host. The induction of an antibody response or a mixed cell-mediated and humoral response is frequently associated with tuberculosis disease or a decrease in the ability to control M. tuberculosis load. We recently reported the induction of similar immune responses and protection by rectal, subcutaneous (SC) or intradermal administration of Mycobacterium bovis BCG in adult mice, guinea pigs and macaques. The rectal immunization, which did not induce the side-effects associated with parenteral routes (axillary adenitis) and which could be used to reduce the risks of viral transmission associated with unsafe injections in the developing world, was analysed and compared in newborn and adult BALB/c mice. The rectal and SC immunization induced, in mice immunized as newborns or as adults, a mixed T helper 1/T helper 2 (Th1/Th2) immune response; however, particularly in adult mice, after SC administration of BCG, the level of Th2 immune response is significantly higher than it is by the rectal route. Six months after immunization with BCG, rectal and SC delivery induced similar levels of protective immunity against a virulent challenge with M. tuberculosis strain (H37Rv) in mice immunized as adults, but the rectal BCG delivery triggered stronger protection than the SC delivery if mice were immunized as newborns.

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“…A plausible reason for this might be the aerosol route of M. tb infection used here, in contrast to the intravenous route of infection used previously (Fortune et al ., ). M. tb infections via the intravenous route tend to result in the earlier appearance of higher bacterial burdens in the spleen compared with infections via the aerosol or intra‐tracheal routes (North et al ., ; de Steenwinkel et al ., ). We surmise that the differences in extrapulmonary dissemination between the espA ::Tn and the 5′ Tn:: pe35 mutants observed here might have been missed, if the mice had been infected intravenously.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA‐independent virulence

Chen

Zhang

Rybniker

et al. 2013

Molecular Microbiology

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SummaryThe type-VII ESX-1 secretion apparatus, encoded by the esx-1 genetic locus, is essential for the export of EsxA and EsxB, two major virulence factors of Mycobacterium tuberculosis. ESX-1 also requires the products of the unlinked espACD operon for optimal function and these proteins are considered integral parts of the secretion apparatus. Here we show that the espACD operon is not necessary for the secretion of EspB, another ESX-1 substrate, and this unimpeded secretion of EspB is associated with significant residual virulence. Upon further investigation, we found that purified EspB can facilitate M. tb virulence even in the absence of EsxA and EsxB, and may do so by binding the bioactive phospholipids phosphatidic acid and phosphatidylserine, both of which are potent bioactive molecules with prominent roles in eukaryotic cell signalling. Our findings provide new insights into the impact of the espACD operon on the ESX-1 apparatus and reveal a distinct virulence function for EspB with novel implications in M. tb-host interactions.

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Vaccinated Mice Remain More Susceptible to Mycobacterium tuberculosis Infection Initiated via the Respiratory Route than via the Intravenous Route

Cited by 9 publications

References 4 publications

Lung cell responses toM. tuberculosisin genetically susceptible and resistant mice following intratracheal challenge

Lung cell responses toM. tuberculosisin genetically susceptible and resistant mice following intratracheal challenge

Development of Mixed Th1/Th2 Type Immune Response and Protection Against Mycobacterium tuberculosis After Rectal or Subcutaneous Immunization of Newborn and Adult Mice with Mycobacterium bovis BCG

Mycobacterium tuberculosis EspB binds phospholipids and mediates EsxA‐independent virulence

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