Distinct<i>H-2</i>complex control of mortality, and immune responses to tuberculosis infection in virgin and BCG-vaccinated mice

Апт, А. С.; Авдиенко, В. Г.; Никоненко, Б. В.; Kramnik, Igor; Moroz, A. M.; Skamene, Emil

doi:10.1111/j.1365-2249.1993.tb03451.x

Cited by 62 publications

(24 citation statements)

References 48 publications

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“…Similarly, other studies have demonstrated necrotic, encapsulated granulomas in mice possessing the sst1 genetic susceptibility locus (34), although encapsulated granulomas were associated with increasing bacterial loads during primary Mtb infection and only associated with low CFU following a course of isoniazid treatment. Similar to other susceptible mouse strains (35-39), the CBA/J mouse can form large coalescing nodular structures during Mtb infection however these are highly associated with end stages of disease, abundant CFU, and substantial lung involvement (not shown). This does however indicate a predisposition to develop fibrotic structures in CBA/J and other susceptible mouse strains that, as we show here, can lead to mature granulomas that are associated with protection in the absence of IL-10.…”

Section: Discussionmentioning

confidence: 77%

IL-10 Inhibits Mature Fibrotic Granuloma Formation during Mycobacterium tuberculosis Infection

Cyktor

Carruthers

Kominsky

et al. 2013

The Journal of Immunology

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Protective immunity and latent Mycobacterium tuberculosis (Mtb) infection in man are associated with the formation of mature protective granulomas within the lung. Unfortunately, understanding the importance of such structures has been hindered by the lack of small animal models that can develop mature granulomas. Here we describe for the first time the formation of mature, fibrotic Mtb-containing pulmonary granulomas in a mouse model of IL-10 deficiency (CBA/J IL-10−/−). Long term control of Mtb infection in the absence of IL-10 was also associated with an early and enhanced capacity for antigen-presentation and a significant increase in the generation of multifunctional T cells. While IL-10 deficiency is known to enhance TH1 immune responses in general, we demonstrate here using transient anti-IL-10R treatment that it is the presence of IL-10 in vivo during the first month of Mtb infection that plays a definitive role in the inhibition of optimum protective immunity that can establish the environment for mature granuloma formation. Although the importance of IL-10 during Mtb infection has been debated, our data demonstrate that in CBA/J mice, IL-10 plays a significant early inhibitory role in preventing the development of protective immunity associated with containment of Mtb infection.

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Section: Discussionmentioning

confidence: 77%

IL-10 Inhibits Mature Fibrotic Granuloma Formation during Mycobacterium tuberculosis Infection

Cyktor

Carruthers

Kominsky

et al. 2013

The Journal of Immunology

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“…It has been demonstrated during the past 15 years that the whole haplotypes and alleles of certain genes within the major histocompatibility complex (MHC) influence susceptibility and immune responses to Mycobacterium tuberculosis in mice [1][2][3][4][5][6] and humans [7][8][9][10][11]. In two independent, genome-wide scans in two different mouse strain combinations, quantitative trait loci (QTL) involved in tuberculosis (TB) severity control were mapped within the H2 complex [12].…”

Section: Introductionmentioning

confidence: 99%

H2 complex controls CD4/CD8 ratio, recurrent responsiveness to repeated stimulations, and resistance to activation-induced apoptosis during T cell response to mycobacterial antigens

Pichugin

Petrovskaya

Apt

2006

Journal of Leukocyte Biology

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Genetic variation in the major histocompatibility complex (MHC) influences susceptibility and immune responses to Mycobacterium tuberculosis in mice and humans, but connections among the severity of tuberculosis (TB), dynamic changes in T cell responses to mycobacteria, and MHC genetic polymorphisms are poorly characterized. The overall effect of the MHC genes on TB susceptibility and cellular responses to mycobacteria is moderate; thus, such studies provide reliable results only if congenic mouse strains bearing a variety of H2 haplotypes on an identical genetic background are analyzed. Using a panel of H2-congenic strains on the B10 background, we demonstrate that T cells from mice of three different strains, which are resistant to TB infection, readily respond by proliferation to repeated stimulations with mycobacterial sonicate, whereas T cells from three susceptible mouse strains die after the second stimulation with antigen. This difference is specific, as T cells from TB-susceptible and -resistant mouse strains do not differ in response to irrelevant antigens. The CD4/CD8 ratio in immune lymph nodes correlates strongly and inversely with TB susceptibility, being significantly lower in resistant mice as a result of an increased content of CD8+ cells. These differences between the two sets of mouse strains correlate with an elevated level of activation-induced T cell apoptosis in TB-susceptible mice and a higher proportion of activated CD44+ CD62 ligand- T cells in TB-resistant mice. These results may shed some light on the nature of the cellular basis of MHC-linked differences in susceptibility to TB.

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“…Indeed, earlier studies have demonstrated that outcomes of vaccination 24, 35–37 and the rate of relapse after chemotherapy 38, 39 are determined by genetic background of the mouse hosts. As no single human represents a genetically diverse population, neither does an individual mouse strain.…”

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confidence: 99%

Man and mouse TB: Contradictions and solutions

Apt

Kramnik

2009

Tuberculosis

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We be of one blood, ye and I Rudyard Kipling, The Jungle BooksAs anyone who has attended tuberculosis research meeting in recent years can attest, disputes about validity of experimental animal models of tuberculosis (TB) erupt frequently, but mostly deteriorate into eloquence matches failing to produce satisfactory conclusions. Funding agencies also join the debate, since translating research into effective measures of TB control in humans is critically dependent on reliable testing of new interventions in animal models. Concerns about the validity of the most popular and accessible mouse model arouse as in some studies robust performance of a vaccine or a drug combination in mice failed to correlate with their efficacy in other species 1 . Here we address controversies that surround the mouse model of tuberculosis and offer a genetic perspective on how to make use of its full power for testing anti-tuberculosis interventions and dissecting pathogenesis of the disease.Much of the information on TB pathogenesis, genetic control and the immune response to infection was obtained in experiments using inbred laboratory mice, which demonstrated that humans and mice are similar in the main features of the innate and adaptive immune responses to mycobacteria, including the protective role of CD4 + T cells, IFN-γ, and TNF-α 2 . As in humans, in the mouse model the pathogen primarily targets the lungs causing a range of pathologies. Availability of unsurpassed genetic resources, which include hundreds of inbred, congenic, recombinant, mutant and genetically engineered strains, and abundance of immunological reagents and methodologies allow in-depth analysis of virtually any aspect of TB pathogenesis in mice, whereas their assortment is scarce for other animal species. Moreover, experiments in mice are less expensive as compared to other species, while genetic standardization further reduces the cost by decreasing individual variation and, hence, numbers of animals in experimental groups. In spite of these advantages, mouse experimental models of TB were repeatedly subjected to substantial criticism as mimicking the human disease with insufficient accuracy. Before we consider the soundness of the statement that TB course in the mouse lung poorly reflect the clinical disease in humans, a simple preamble on how principles of biological diversity are applied to humans and mice in TB studies is needed.Genetic heterogeneity is a fundamental property of all animal species, and it accounts for a considerable fraction of intraspecies variation in susceptibility to and severity of mycobacterial infections typical for all mammals (reviewed in 3, 4 ). Introductory sections of virtually all TB papers contain trivial sentences that: (i) only a small per cent of individuals infected with virulent M. tuberculosis develop clinical signs of infection; and (ii) infection can result in divergent outcomes in different individuals, ranging from spontaneous eradication, latent nonPublisher's Disclaimer: This is a PDF file of an unedited manusc...

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DistinctH-2complex control of mortality, and immune responses to tuberculosis infection in virgin and BCG-vaccinated mice

Cited by 62 publications

References 48 publications

IL-10 Inhibits Mature Fibrotic Granuloma Formation during Mycobacterium tuberculosis Infection

IL-10 Inhibits Mature Fibrotic Granuloma Formation during Mycobacterium tuberculosis Infection

H2 complex controls CD4/CD8 ratio, recurrent responsiveness to repeated stimulations, and resistance to activation-induced apoptosis during T cell response to mycobacterial antigens

Man and mouse TB: Contradictions and solutions

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