Fcγ Receptors Regulate Immune Activation and Susceptibility during <i>Mycobacterium tuberculosis</i> Infection

Maglione, Paul J.; Xu, Jiayong; Casadevall, Arturo; Chan, John

doi:10.4049/jimmunol.180.5.3329

Cited by 133 publications

(158 citation statements)

References 54 publications

(83 reference statements)

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“…Only modestly increased transcription of Fc receptors and genes of the MHC-I antigen presentation pathway were detected. Transcription of the inhibitory Fc receptor FcGR2B was induced in WT and iNOS -/-mice which is associated with susceptibility to M.tb [16]. Since activating Fc receptors were induced in a similar or stronger fashion, inhibitory FcGR2B signalling effects could be compensated for on a cellular level.…”

Section: Resultsmentioning

confidence: 84%

See 1 more Smart Citation

Combination of host susceptibility and Mycobacterium tuberculosis virulence define gene expression profile in the host

Beisiegel¹,

Mollenkopf²,

Hahnke³

et al. 2009

Eur J Immunol

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Progression and outcome of tuberculosis is governed by extensive crosstalk between pathogen and host. Analyses of global changes in gene expression during immune response to infection with Mycobacterium tuberculosis (M.tb) can help identify molecular markers of disease state and progression. Global distribution of M.tb strains with different degrees of virulence and drug resistance, especially for the immunocompromised host, make closer analyses of host responses more pressing than ever. Here, we describe global transcriptional responses of inducible nitric oxide synthase-deficient (iNOS -/-) and WT mice infected with two related M.tb strains of markedly different virulence, namely the M.tb laboratory strains H37Rv and H37Ra. Both hosts exhibited highly similar resistance to infection with H37Ra. In contrast, iNOS -/-mice rapidly succumbed to H37Rv, whereas WT mice developed chronic course of disease. By differential analyses, virulence-specific changes in global host gene expression were analyzed to identify molecular markers characteristic for chronic versus acute infection. We identified several markers unique for different stages of disease progression and not previously associated with virulencespecific host responses in tuberculosis.

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Section: Resultsmentioning

confidence: 84%

“…The role of B cells and antibodies during TB has recently gained renewed interest [16]. Elevated IgG-related gene transcription in H37Rv-infected iNOS -/-mice emphasizes a role for these genes in severe inflammation during TB.…”

Section: Adaptive Immune Responsementioning

confidence: 99%

Combination of host susceptibility and Mycobacterium tuberculosis virulence define gene expression profile in the host

Beisiegel¹,

Mollenkopf²,

Hahnke³

et al. 2009

Eur J Immunol

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“…The role for B cells and humoral immunity in protection against Mtb infection is an emerging area of research, as some components of the humoral immune response such as Fc receptors (57) have been shown to impact immune responses to TB. Importantly, B cell follicles containing proliferating B cells have been found to colocalize with T cells within human TB granulomas (3, 7), A-TB in NHPs (4), and Mtb-infected mouse granulomas (18,19).…”

Section: Methodsmentioning

confidence: 99%

CXCR5+ T helper cells mediate protective immunity against tuberculosis

Slight¹,

Rangel-Moreno²,

Gopal³

et al. 2013

J. Clin. Invest.

182

293

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One third of the world's population is infected with Mycobacterium tuberculosis (Mtb). Although most infected people remain asymptomatic, they have a 10% lifetime risk of developing active tuberculosis (TB). Thus, the current challenge is to identify immune parameters that distinguish individuals with latent TB from those with active TB. Using human and experimental models of Mtb infection, we demonstrated that organized ectopic lymphoid structures containing CXCR5 + T cells were present in Mtb-infected lungs. In addition, we found that in experimental Mtb infection models, the presence of CXCR5 + T cells within ectopic lymphoid structures was associated with immune control. Furthermore, in a mouse model of Mtb infection, we showed that activated CD4 + CXCR5 + T cells accumulated in Mtb-infected lungs and produced proinflammatory cytokines. Mice deficient in Cxcr5 had increased susceptibility to TB due to defective T cell localization within the lung parenchyma. We demonstrated that CXCR5 expression in T cells mediated correct T cell localization within TB granulomas, promoted efficient macrophage activation, protected against Mtb infection, and facilitated lymphoid follicle formation. These data demonstrate that CD4 + CXCR5 + T cells play a protective role in the immune response against TB and highlight their potential use for future TB vaccine design and therapy.

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“…FcR signaling in the regulation of the CD4 ϩ T-cell-mediated inflammatory response has been reported in the case of Schistosoma mansoni (25), since both B-cell-deficient mice and FcR Ϫ/Ϫ mice showed markedly exacerbated hepatic granuloma formation and failed to downmodulate the pathology during the chronic stage of the disease. An FcR-dependent mechanism to regulate the T-cell response against M. tuberculosis has recently been confirmed (30).…”

Section: (Ii) Fcrmentioning

confidence: 94%

B Cells Are Essential for Moderating the Inflammatory Response and Controlling Bacterial Multiplication in a Mouse Model of Vaccination againstChlamydophila abortusInfection

Buendía¹,

Ortega

Caro

et al. 2009

Infect Immun

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The use of inactivated vaccines associated with suitable adjuvants has been demonstrated to confer a good level of protection against Chlamydophila abortus. However, the basis of the immune protective response induced by these vaccines has been poorly studied. B cells act as an immune regulatory population during primary infection by C. abortus. Thus, it was considered of interest to study the role of B cells in an infection after immunization with a killed vaccine. For this, C57BL/6 and B-cell-deficient mice were immunized with a killed vaccine against C. abortus using QS-21 as the adjuvant. After challenge, the course of infection was established by analysis of morbidity, C. abortus burden in the liver, and histopathological changes. The immune response induced was studied by real-time PCR techniques. Experiments involving transfer of immune serum from vaccinated or previously infected mice were also carried out. The lack of B cells reduced the protection conferred by the QS-21 adjuvant vaccine. Vaccinated B-cell-deficient mice showed a 1,000-fold-greater bacterial burden in the liver than their wild-type counterparts. Obvious differences existed in the liver, where a severe neutrophilic reaction and extended areas of necrosis were observed with vaccinated B-cell-deficient mice. An analysis of the immune response pointed to a significant increase in inflammatory cytokines and chemokines and the deficient production of transforming growth factor beta. The transfer of antibodies restored the level of protection. This study demonstrates that B cells play a crucial role in controlling C. abortus multiplication and prevent an exacerbated inflammatory response.

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Fcγ Receptors Regulate Immune Activation and Susceptibility during Mycobacterium tuberculosis Infection

Cited by 133 publications

References 54 publications

Combination of host susceptibility and Mycobacterium tuberculosis virulence define gene expression profile in the host

Combination of host susceptibility and Mycobacterium tuberculosis virulence define gene expression profile in the host

CXCR5+ T helper cells mediate protective immunity against tuberculosis

B Cells Are Essential for Moderating the Inflammatory Response and Controlling Bacterial Multiplication in a Mouse Model of Vaccination againstChlamydophila abortusInfection

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