Systemic Mycobacterium kansasii infection and regulation of the alloantigenic response

Collins, Frank M.; Cunningham, Dean S.

doi:10.1128/iai.32.2.614-624.1981

Cited by 39 publications

(15 citation statements)

References 16 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chemical analysis showed that the rough variants were lacking in lipooligosaccharides. Importantly, the investigators were able to relate this work to an earlier study on the pathogenicity of these M. kansasii strains in mice (13), leading to the conclusion that pathogenic strains had a rough phenotype. This finding is consistent with our observations for M. abscessus-R and M. abscessus-S.…”

Section: Discussionmentioning

confidence: 89%

Preliminary Characterization of a Mycobacterium abscessus Mutant in Human and Murine Models of Infection

1999

View full text Add to dashboard Cite

The ability to persist in the host after the establishment of infection is an important virulence determinant for mycobacteria.Mycobacterium abscessus is a rapidly growing mycobacterial species which causes a variety of clinical syndromes in humans. We have obtained a rough, wild-type human clinical isolate of M. abscessus (M. abscessus-R) and a smooth, attenuated mutant(M. abscessus-S) which spontaneously dissociated from the clinical isolate. We have found that M. abscessus-R is able to persist and multiply in a murine pulmonary infection model in contrast to M. abscessus-S, which is rapidly cleared. To understand the basis for this difference, we characterized the behavior of these variants in human tissue culture models of infection. M. abscessus-R is able to persist and multiply in human monocytes, while M. abscessus-S is deficient in this ability. Both of these variants are phagocytized by human monocytes. M. abscessus-R resides in a phagosome typical for pathogenic mycobacteria with a tightly adherent phagosomal membrane. In contrast,M. abscessus-S resides in a “loose” phagosome with the phagosomal membrane separated from the bacterial cell wall. BothM. abscessus variants also have distinctive growth patterns in a recently described fibroblast-mycobacterium microcolony assay, with M. abscessus-R exhibiting growth characteristics similar to those previously reported for virulent M. tuberculosis and M. abscessus-S exhibiting growth characteristics similar to those previously reported for avirulentM. tuberculosis. In both the monocyte infection assay and the murine pulmonary infection model, numerous infected mononuclear phagocyte aggregates develop at sites of M. abscessus-Rinfection, but are absent with M. abscessus-S infection. We conclude that a mutation has occurred in the M. abscessus-Svariant which has altered the ability of this organism to persist and multiply in host cells and that this may be related to the phenotypic changes we have observed in our tissue culture models of infection.

show abstract

Section: Discussionmentioning

confidence: 89%

Preliminary Characterization of a Mycobacterium abscessus Mutant in Human and Murine Models of Infection

1999

View full text Add to dashboard Cite

show abstract

“…Earlier studies showed that rough variants of M. kansasii, devoid of all LOSs, cause chronic systemic infections in mice. In contrast, smooth variants containing LOSs are rapidly cleared from the organs of infected animals (Collins and Cunningham, 1981;Belisle and Brennan, 1989). It was suggested that LOSs might be an avirulence factor, which masks the effect of other cell wall lipid components that are important for virulence (Belisle and Brennan, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…However, no correlation between the presence of LOSs and the colony morphology of the strains has been observed in either M. tuberculosis (Lemassu et al, 1992) or M. gastri (Gilleron et al, 1993). The role of LOSs in mycobacterial virulence is not clear (Collins and Cunningham, 1981;Belisle and Brennan, 1989;Besra et al, 1992), primarily because of the lack of isogenic mycobacterial strains deficient in their production. As such, the precise contribution of LOSs to pathogenesis or virulence cannot be evaluated and their biological activities in an infected host cannot be directly tested.…”

Section: Introductionmentioning

confidence: 99%

Identification of the lipooligosaccharide biosynthetic gene cluster from Mycobacterium marinum

Ren

Dover

Islam

et al. 2007

Molecular Microbiology

128

View full text Add to dashboard Cite

SummaryLipooligosaccharides (LOSs) are antigenic glycolipids that are present in some species of Mycobacterium including the Canetti strain of M. tuberculosis. The core LOS structures from several mycobacterial organisms have been established, but the biosynthetic pathways of LOSs remain unknown. In this study, we describe two transposon insertion mutants of M. marinum that exhibit altered colony morphology. Cell wall analysis reveals that the MRS1271 mutant is defective in the synthesis of LOS-II, whereas the MRS1178 mutant accumulates an intermediate between LOS-I and -II. The genetic lesions were localized to two genes, MM2309 and MM2332. MM2309 encodes a UDP-glucose dehydrogenase that is involved in the synthesis of D-xylose. MM2332 is predicted to encode a decarboxylase. These two genes and a previously identified losA gene are localized in a gene cluster likely to be involved in the biosynthesis of LOSs. Our results also show that LOSs play an important role in sliding motility, biofilm formation, and infection of host macrophages. Taken together, our studies have identified, for the first time, a LOS biosynthetic locus. This is an important step in assessing the differential distribution of LOSs among Mycobacterium species and understanding the role of LOSs in mycobacterial virulence.

show abstract

“…Moreover, at this late stage of infection, some suppressive material (factor or cell or both) might appear which would inhibit the proliferation of T helper cells and would be associated with the defect in IL2 production. It has previously been shown that mice infected with various species of mycobacteria have splenic suppressor cells, either T cells (10,33) or macrophages (16,33), which can inhibit in vitro T cell-mediated responses (15,39).…”

Section: Discussionmentioning

confidence: 99%

Deficit of interleukin 2 production associated with impaired T-cell proliferative responses in Mycobacterium lepraemurium infection

Hoffenbach¹,

Lagrange²,

Bach³

1983

Infect Immun

View full text Add to dashboard Cite

C57BL/6 and BALB/c mice were infected intravenously with 10(7) Mycobacterium lepraemurium (MLM). At various times after infection, spleen cells were tested for their capacity to proliferate in vitro in response to concanavalin A (ConA) and to allogeneic cells. The generation of alloreactive cytotoxic T lymphocytes was also studied. The mitogen- and allogeneic-cell-induced blastogenesis of splenocytes from MLM-infected C57BL/6 and BALB/c mice was shown to be depressed during infection. The maximal decrease occurred 6 months after infection. Conversely, no reduction in the ability to generate alloreactive cytotoxic T lymphocytes was observed even after 6 months of infection. At the same time, interleukin 2 (IL2) activity generated by ConA stimulation of infected splenocytes was measured in both strains. IL2 activity in the ConA-stimulated culture supernatants was decreased as early as 1 month after MLM inoculation as compared with supernatants from age-matched control mice. Thus, IL2 production by infected-mouse spleen cells was shown to decline earlier than their proliferative responses to ConA and to allogeneic cells. ConA-induced T-cell blasts from infected mice showed a reduced ability to proliferate when incubated with an IL2-containing reference supernatant from ConA-stimulated normal spleen cells. These data suggest that a defect in IL2 production and utilization might contribute to the impairment of T cell-mediated immunity observed in MLM-infected mice.

show abstract

Systemic Mycobacterium kansasii infection and regulation of the alloantigenic response

Cited by 39 publications

References 16 publications

Preliminary Characterization of a Mycobacterium abscessus Mutant in Human and Murine Models of Infection

Preliminary Characterization of a Mycobacterium abscessus Mutant in Human and Murine Models of Infection

Identification of the lipooligosaccharide biosynthetic gene cluster from Mycobacterium marinum

Deficit of interleukin 2 production associated with impaired T-cell proliferative responses in Mycobacterium lepraemurium infection

Contact Info

Product

Resources

About