Differential Organization of the Local Immune Response in Patients with Active Cavitary Tuberculosis or with Nonprogressive Tuberculoma

Ulrichs, Timo; Kosmiadi, George A.; Jörg, Sabine; Pradl, Lydia; Titukhina, Marina; Mishenko, Vladimir; Gushina, Nadya; Kaufmann, Stefan H. E.

doi:10.1086/430621

Cited by 116 publications

(100 citation statements)

References 36 publications

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“…In contrast, the wall composition of cavities in patients with active pulmonary TB presents a diffuse pattern of proliferating cells (Figure 4), suggesting insufficient coordination. Re-stimulation of collagenase-extracted cells from both patient groups in vitro revealed that they produce high amounts of IFN-γ upon specific stimulation with mycobacterial antigens [27], confirming earlier in situ data [16]. Kaplan et al also described abundant IFN-γ production in cavity walls from patients who failed to control TB [28].…”

Section: The Immune Response In Progressive and Non-progressive Tubersupporting

confidence: 64%

“…Whereas cavitary TB patients presented patterns of low vascularization in the areas of peripheral infiltration, tuberculoma lesions were always surrounded by highly vascularized tissue [27]. In addition, the periphery of tuberculoma lesions exhibited higher proliferative activity, compared with regions in cavitary TB lesions.…”

Section: The Immune Response In Progressive and Non-progressive Tubermentioning

confidence: 88%

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New insights into the function of granulomas in human tuberculosis

Ulrichs

Kaufmann

2005

The Journal of Pathology

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343

337

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The human tuberculous granuloma provides the morphological framework for local immune processes central to the outcome of tuberculosis. This review article describes investigations on human lung granulomas aimed at better understanding the regional host response and counter-measures to Mycobacterium tuberculosis. These findings lead to a revised view of the regional immune response in human tuberculosis. Novel insights into this dynamic cross-talk form the basis of novel intervention strategies.

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Section: The Immune Response In Progressive and Non-progressive Tubersupporting

confidence: 64%

Section: The Immune Response In Progressive and Non-progressive Tubermentioning

confidence: 88%

New insights into the function of granulomas in human tuberculosis

Ulrichs

Kaufmann

2005

The Journal of Pathology

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343

337

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“…Evidence supporting this comes from a study in which granuloma wall structures of human TB patients with latent or active disease were compared [12]. Granuloma wall structures in latently infected individuals were composed of repeating units of lymphoid follicles containing numerous proliferating lymphocytes, whereas wall structures in patients with active disease contained few proliferating lymphocytes and no lymphoid aggregates.…”

Section: Discussionmentioning

confidence: 99%

“…In a study comparing pathology of human patients with active versus latent TB, presence of lymphoid follicles in granulomatous tissue was associated with immune control whereas absence of such structures was found in patients with active TB disease [12]. These findings suggest that local lymphocyte activation may be crucial in mediating containment of infection during latent TB.…”

Section: Introductionmentioning

confidence: 92%

Secondary lymphoid organs are dispensable for the development of T‐cell‐mediated immunity during tuberculosis

et al. 2010

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Tuberculosis causes 2 million deaths per year, yet in most cases the immune response successfully contains the infection and prevents disease outbreak. Induced lymphoid structures associated with pulmonary granuloma are observed during tuberculosis in both humans and mice and could orchestrate host defense. To investigate whether granuloma perform lymphoid functions, mice lacking secondary lymphoid organs (SLO) were infected with Mycobacterium tuberculosis (MTB). As in WT mice, granuloma developed, exponential growth of MTB was controlled, and antigen-specific T-cell responses including memory T cells were generated in the absence of SLO. Moreover, adoptively transferred T cells were primed locally in lungs in a granuloma-dependent manner. T-cell activation was delayed in the absence of SLO, but resulted in a normal development program including protective subsets and functional recall responses that protected mice against secondary MTB infection. Our data demonstrate that protective immune responses can be generated independently of SLO during MTB infection and implicate local pulmonary T-cell priming as a mechanism contributing to host defense.Key words: Granuloma . Lymphoid neogenesis . T-cell development . Tuberculosis Supporting Information available online IntroductionMycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), currently persists in one-third of the world's population [1]. In most cases, the immune response generated upon exposure contains, but does not eradicate, the bacilli and an asymptomatic persistent infection develops, termed latent TB. Approximately one in ten latently infected individuals undergo reactivation to active TB disease during their lifetime. However, Ã These authors contributed equally to this work. ÃÃ These authors share equal senior authorship. [2,3]. Granuloma are considered central for control of MTB as loss of granuloma structure is associated with poor disease outcome in humans and animal models [3,4]. Yet, the precise mechanisms by which granuloma mediate control of MTB are poorly understood. Induction of an adaptive immune response is essential for host protection against MTB. Antigen-specific T-cell responses are generated within secondary lymphoid organs (SLO), such as lymph nodes (NO) and spleen. SLO maximize efficiency of encounters between APC and naïve T lymphocytes [5]. Therefore, SLO are critical for the generation of adaptive immunity. Ectopic accumulations of lymphoid cells, known as tertiary lymphoid organs, sometimes arise during chronic inflammation or infection. Tertiary lymphoid organs resemble SLO in structure and cell composition and evidence exists that some are capable of generating adaptive immunity [5,6]. However, whether immune responses generated outside of SLO are truly effective and thus beneficial in defense against pathogens is unclear.Recent reports have described lymphoid features associated with murine and human granuloma, such as B-cell follicles and the peripheral node addressin, which is expressed on high endothel...

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“…A recent meta-analysis suggests that the active phase of untreated pulmonary TB from the onset of symptoms to cure or death lasts for, on average, three years, but with considerable variation (Tiemersma et al, 2011). About 90% of modern human TB infections are clinically latent, with the pathogen being contained within granulomatous lesions at the site of the primary infection (Ulrichs et al, 2005). Spinal involvement occurs in only a small fraction of patients with TB (e.g.…”

Section: Rationale Of the Studymentioning

confidence: 99%

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy)

Sparacello

Roberts

Canci

et al. 2016

International Journal of Paleopathology

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Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. Abstract: The aim of this research was to gain insights on the timeline of progression of osteoarticular tuberculosis (TB) in people from the Neolithic period by using skeletal traits that are independent of the bony lesions. The body proportions and postcranial mechanical strength of bones from two individuals from Liguria in northwestern Italy (Arene Candide 5, adolescent, and Arma dell'Aquila 1, adult), were compared with the rest of the Ligurian Neolithic skeletal series (45 individuals). If TB led to wasting of the skeleton and lack of normal function which endured for years, as often happens today, a clear signature of postcranial gracility and disruption of development should be apparent. Conversely, rapid progress of the disease would leave little systemic macroscopic change in the skeleton, except for the bony lesions directly caused by the TB pathogen, suggesting a different level of bacterial virulence in the past. The extreme biomechanical gracility observed in the lower limb of Arene Candide 5 suggests a period of compromised diaphyseal periosteal apposition during ontogeny due to metabolic disturbances likely linked to TB. Results suggest that, in Neolithic Liguria, TB in humans saw a slow, chronic progression, which is characteristic of diseases with long histories of host-pathogen coevolution. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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Differential Organization of the Local Immune Response in Patients with Active Cavitary Tuberculosis or with Nonprogressive Tuberculoma

Cited by 116 publications

References 36 publications

New insights into the function of granulomas in human tuberculosis

New insights into the function of granulomas in human tuberculosis

Secondary lymphoid organs are dispensable for the development of T‐cell‐mediated immunity during tuberculosis

Insights on the paleoepidemiology of ancient tuberculosis from the structural analysis of postcranial remains from the Ligurian Neolithic (northwestern Italy)

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