Changes in T‐Lymphocyte Subsets in Lungs and Spleens of Mice with Slowly Progressive Primary <i>Mycobacterium tuberculosis</i> Infection: Involvement of Unconventional T‐Cell Subsets

Phyu,; Sørnes,; Mustafa,; Tadesse,; Jønsson,; Bjune,

doi:10.1046/j.1365-3083.1999.00563.x

Cited by 7 publications

(9 citation statements)

References 33 publications

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“…49,72,73 Interleukin-17-producing cd T cells are also found in M. tuberculosis-infected tissue, although their function is rarely investigated. 74,75 We did not detect significant IL-17A expression in liver and spleen tissue, nor did we find M. avium-specific Th17 or increased numbers of cd T cells in spleens of infected mice. The absence of Th17 cell differentiation might possibly be a result of raised levels of IFN-c, which has also been implicated as a negative regulator of antigen-specific Th17 development during primary bacillus Calmette-Gu erin infection.…”

Section: Discussioncontrasting

confidence: 55%

“…The most prominent source is CD4 + Th17 cells that seem more important in memory responses and vaccine‐induced immunity than in control of primary M. tuberculosis . Interleukin‐17‐producing γδ T cells are also found in M. tuberculosis ‐infected tissue, although their function is rarely investigated . We did not detect significant IL‐17A expression in liver and spleen tissue, nor did we find M. avium ‐specific Th17 or increased numbers of γδ T cells in spleens of infected mice.…”

Section: Discussionmentioning

confidence: 53%

“…The absence of Th17 cell differentiation might possibly be a result of raised levels of IFN‐γ, which has also been implicated as a negative regulator of antigen‐specific Th17 development during primary bacillus Calmette–Guérin infection . The decrease in relative γδ T cell frequency might be explained by expansion of activated αβ T cells as previously described in mouse M. tuberculosis infections …”

Section: Discussionmentioning

confidence: 77%

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Dynamics of immune effector mechanisms during infection with Mycobacterium avium in C57BL/6 mice

et al. 2013

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SummaryOpportunistic infections with non-tuberculous mycobacteria such as Mycobacterium avium are receiving renewed attention because of increased incidence and difficulties in treatment. As for other mycobacterial infections, a still poorly understood collaboration of different immune effector mechanisms is required to confer protective immunity. Here we have characterized the interplay of innate and adaptive immune effector mechanisms contributing to containment in a mouse infection model using virulent M. avium strain 104 in C57BL/6 mice. M. avium caused chronic infection in mice, as shown by sustained organ bacterial load. In the liver, bacteria were contained in granuloma-like structures that could be defined morphologically by expression of the antibacterial innate effector protein Lipocalin 2 in the adjoining hepatocytes and infiltrating neutrophils, possibly contributing to containment. Circulatory antimycobacterial antibodies steadily increased throughout infection and were primarily of the IgM isotype. Highest levels of interferon-c were found in infected liver, spleen and serum of mice approximately 2 weeks post infection and coincided with a halt in organ bacterial growth. In contrast, expression of tumour necrosis factor was surprisingly low in spleen compared with liver. We did not detect interleukin-17 in infected organs or M. avium-specific T helper 17 cells, suggesting a minor role for T helper 17 cells in this model. A transient and relative decrease in regulatory T cell numbers was seen in spleens. This detailed characterization of M. avium infection in C57BL/6 mice may provide a basis for future studies aimed at gaining better insight into mechanisms leading to containment of infections with non-tuberculous mycobacteria.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 77%

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Dynamics of immune effector mechanisms during infection with Mycobacterium avium in C57BL/6 mice

et al. 2013

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“…We have previously established a mouse model of slowly progressive primary tuberculosis [17,18]. Mice infected intraperitoneally (i.p.)…”

Section: Introductionmentioning

confidence: 99%

In Situ Expression of Cytokines and Cellular Phenotypes in the Lungs of Mice with Slowly Progressive Primary Tuberculosis

Mustafa

Phyu²,

Nilsen³

et al. 2000

Scand J Immunol

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51:548±556The cellular phenotypes and the expression of cytokines were studied in the lungs of mice, using immunohistochemistry, during different phases of slowly progressive primary murine tuberculosis infection. During the ®rst phase the small focal lesions in healthy mice contained predominantly interleukin-2 (IL-2)-expressing cells. A small number of tumour necrosis factor-a (TNF-a)-, monocyte chemoattractant protein-1 (MCP-1)-and IL-10-expressing cells were also present. IL-4-expressing cells were not detected. During the second phase the mice became unwell, but the bacterial counts and the size of focal lesions stabilized. IL-4-expressing cells appeared. The IL-10-, TNF-a-and MCP-1-expressing cells increased in number. On progression to phase three, the mice became seriously unwell and died rapidly. The in¯ammation spread to < 80% of the lung parenchyma. There was a marked increase in the number of IL-10-expressing cells. Expression of other cytokines was similar to that observed in the second phase. In the lesions, 3±6% of the macrophages (Mf) containing mycobacterial antigens expressed high levels of IL-10 and TNF-a. The absolute numbers of CD3-, CD4-and CD11b-expressing cells in the lesions increased with the progression of infection. The numbers of CD8 cells were reduced in the last phase of infection. The kinetics of T-lymphocyte subsets and the pattern of cytokine expression changed with the type and degree of tissue injury. The small number of Mf with a heavy load of mycobacterial antigens may be the cause of this disturbance in cytokine balance, thus leading to progression of in¯ammation.

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“…The lung derived cells were immunotyped for the Th1-transcription markers T-bet, CXCR3 and intracellular IFN-γ as previously described [19]. Total lung cells were counted before staining and the numbers of T cells positive for markers were enumerated using flow cytometry [19] [43] [44]. …”

Section: Methodsmentioning

confidence: 99%

The ΔfbpA attenuated candidate vaccine from Mycobacterium tuberculosis, H37Rv primes for a stronger T-bet dependent Th1 immunity in mice

Roche¹,

Smith²,

Lindsey³

et al. 2011

Tuberculosis

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Summary The ΔfbpA candidate vaccine derived from Mycobacterium tuberculosis (H37Rv) protects mice better than BCG against tuberculosis, and we investigated the hypothesis that ΔfbpA may induce a stronger Th1 immunity. Since T-bet transcription factor regulates Th1 immunity, mice infected with ΔfbpA, BCG vaccine and related mycobacteria were analyzed for T-bet positive T cells. Mouse dendritic cells (DCs) or macrophages were also pulsed with excretory-secreted antigens (ES; Antigen-85B, ESAT-6 and CFP10) and cocultured with T cells from immunized or naïve mice and tested for in vitro induction of T-bet and IFN-γ. In both models, ΔfbpA mutant induced a stronger response of T-bet+CD4 T cells, which correlated with an increased expansion of IFN-γ+CD4 T cells in vivo and in vitro. When DCs pulsed with ES antigens were allowed to stimulate T cells, ESAT-6 and CFP-10 failed to induce a recall expansion of T-bet+IFN-γ+CD4 T cells from BCG vaccinated mice. Thus, deletion of RD1 in BCG seems to reduce its ability to induce T-bet and induce stronger Th1 immunity. Finally, mice were vaccinated with ΔfbpA and BCG and challenged with virulent Mtb for evaluation of protection and T cell expansion. ΔfbpA vaccinated mice showed a rapid and stronger expansion of CD4+CXCR3+ IFN-γ+ T cells in the lungs of Mtb challenged mice, compared to those which had BCG vaccine. ΔfbpA immunized mice also showed a better decline of the Mtb bacterial counts of the lungs. Mtb derived ΔfbpA candidate vaccine therefore induces qualitatively better T-bet dependent Th1 immunity than BCG vaccine.

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Changes in T‐Lymphocyte Subsets in Lungs and Spleens of Mice with Slowly Progressive Primary Mycobacterium tuberculosis Infection: Involvement of Unconventional T‐Cell Subsets

Cited by 7 publications

References 33 publications

Dynamics of immune effector mechanisms during infection with Mycobacterium avium in C57BL/6 mice

Dynamics of immune effector mechanisms during infection with Mycobacterium avium in C57BL/6 mice

In Situ Expression of Cytokines and Cellular Phenotypes in the Lungs of Mice with Slowly Progressive Primary Tuberculosis

The ΔfbpA attenuated candidate vaccine from Mycobacterium tuberculosis, H37Rv primes for a stronger T-bet dependent Th1 immunity in mice

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