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Host genetics in granuloma formation: human-like lung pathology in mice with reciprocal genetic susceptibility to M. tuberculosis and M. avium.

Kondratieva E, Logunova N, Majorov K, Averbakh M, Apt A - PLoS ONE (2010)

Bottom Line: The role of host genetics in granuloma formation is not well defined.Necrotizing granuloma surrounded by hypoxic zones, as well as a massive neutrophil influx, develop in the lungs of M. avium-infected B6 mice and in the lungs of M. tuberculosis-infected I/St mice, but not in the lungs of corresponding genetically resistant counterparts.The mirror-type lung tissue responses to two virulent mycobacteria indicate that the level of genetic susceptibility of the host to a given mycobacterial species largely determines characteristics of pathology, and directly demonstrate the importance of host genetics in pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow, Russia.

ABSTRACT
Development of lung granulomata is a hallmark of infections caused by virulent mycobacteria, reflecting both protective host response that restricts infection spreading and inflammatory pathology. The role of host genetics in granuloma formation is not well defined. Earlier we have shown that mice of the I/St strain are extremely susceptible to Mycobacterium tuberculosis but resistant to M. avium infection, whereas B6 mice show a reversed pattern of susceptibility. Here, by directly comparing: (i) characteristics of susceptibility to two infections in vivo; (ii) architecture of lung granulomata assessed by immune staining; and (iii) expression of genes encoding regulatory factors of neutrophil influx in the lung tissue, we demonstrate that genetic susceptibility of the host largely determines the pattern of lung pathology. Necrotizing granuloma surrounded by hypoxic zones, as well as a massive neutrophil influx, develop in the lungs of M. avium-infected B6 mice and in the lungs of M. tuberculosis-infected I/St mice, but not in the lungs of corresponding genetically resistant counterparts. The mirror-type lung tissue responses to two virulent mycobacteria indicate that the level of genetic susceptibility of the host to a given mycobacterial species largely determines characteristics of pathology, and directly demonstrate the importance of host genetics in pathogenesis.

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The picture of leukocyte infiltration of the lung tissue of I/St (left) and B6 (right) mice infected with 2×103 CFU of M. avium via aerosol route 8 weeks earlier.Peroxidase immune staining with hematoxylin counter-staining (×150). Cell populations are indicated on the left side. See text for the description.
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pone-0010515-g002: The picture of leukocyte infiltration of the lung tissue of I/St (left) and B6 (right) mice infected with 2×103 CFU of M. avium via aerosol route 8 weeks earlier.Peroxidase immune staining with hematoxylin counter-staining (×150). Cell populations are indicated on the left side. See text for the description.

Mentions: In our recent studies we have characterized the general picture of lung pathology in M. avium-infected B6 and I/St mice [15], as well as the cellular composition of lung lesions in M. tuberculosis-infected I/St mice [10]. In order to complete our analysis of pathology caused by the two mycobacterial species in genetically susceptible and resistant hosts, we compared dynamic pictures of lung infiltration with lymphoid cells in M. avium-infected B6 and I/St mice. Immune staining of the lung tissue sections for CD4+ and CD8+ T cells, CD19+ B cells and Ly-6G+ PMN was performed at weeks 8 (Fig. 2) and 16 (Fig. 3) post-infection, and the following major differences between susceptible and resistant mice were observed.


Host genetics in granuloma formation: human-like lung pathology in mice with reciprocal genetic susceptibility to M. tuberculosis and M. avium.

Kondratieva E, Logunova N, Majorov K, Averbakh M, Apt A - PLoS ONE (2010)

The picture of leukocyte infiltration of the lung tissue of I/St (left) and B6 (right) mice infected with 2×103 CFU of M. avium via aerosol route 8 weeks earlier.Peroxidase immune staining with hematoxylin counter-staining (×150). Cell populations are indicated on the left side. See text for the description.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2865535&req=5

pone-0010515-g002: The picture of leukocyte infiltration of the lung tissue of I/St (left) and B6 (right) mice infected with 2×103 CFU of M. avium via aerosol route 8 weeks earlier.Peroxidase immune staining with hematoxylin counter-staining (×150). Cell populations are indicated on the left side. See text for the description.
Mentions: In our recent studies we have characterized the general picture of lung pathology in M. avium-infected B6 and I/St mice [15], as well as the cellular composition of lung lesions in M. tuberculosis-infected I/St mice [10]. In order to complete our analysis of pathology caused by the two mycobacterial species in genetically susceptible and resistant hosts, we compared dynamic pictures of lung infiltration with lymphoid cells in M. avium-infected B6 and I/St mice. Immune staining of the lung tissue sections for CD4+ and CD8+ T cells, CD19+ B cells and Ly-6G+ PMN was performed at weeks 8 (Fig. 2) and 16 (Fig. 3) post-infection, and the following major differences between susceptible and resistant mice were observed.

Bottom Line: The role of host genetics in granuloma formation is not well defined.Necrotizing granuloma surrounded by hypoxic zones, as well as a massive neutrophil influx, develop in the lungs of M. avium-infected B6 mice and in the lungs of M. tuberculosis-infected I/St mice, but not in the lungs of corresponding genetically resistant counterparts.The mirror-type lung tissue responses to two virulent mycobacteria indicate that the level of genetic susceptibility of the host to a given mycobacterial species largely determines characteristics of pathology, and directly demonstrate the importance of host genetics in pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Immunogenetics, Central Institute for Tuberculosis, Moscow, Russia.

ABSTRACT
Development of lung granulomata is a hallmark of infections caused by virulent mycobacteria, reflecting both protective host response that restricts infection spreading and inflammatory pathology. The role of host genetics in granuloma formation is not well defined. Earlier we have shown that mice of the I/St strain are extremely susceptible to Mycobacterium tuberculosis but resistant to M. avium infection, whereas B6 mice show a reversed pattern of susceptibility. Here, by directly comparing: (i) characteristics of susceptibility to two infections in vivo; (ii) architecture of lung granulomata assessed by immune staining; and (iii) expression of genes encoding regulatory factors of neutrophil influx in the lung tissue, we demonstrate that genetic susceptibility of the host largely determines the pattern of lung pathology. Necrotizing granuloma surrounded by hypoxic zones, as well as a massive neutrophil influx, develop in the lungs of M. avium-infected B6 mice and in the lungs of M. tuberculosis-infected I/St mice, but not in the lungs of corresponding genetically resistant counterparts. The mirror-type lung tissue responses to two virulent mycobacteria indicate that the level of genetic susceptibility of the host to a given mycobacterial species largely determines characteristics of pathology, and directly demonstrate the importance of host genetics in pathogenesis.

Show MeSH
Related in: MedlinePlus