Interferon‐αβ mediates partial control of early pulmonary <i>Mycobacterium bovis</i> bacillus Calmette–Guérin infection

Kuchtey, John; Fulton, Scott A.; Reba, Scott M.; Boom, W. Henry

doi:10.1111/j.1365-2567.2006.02337.x

Cited by 35 publications

(30 citation statements)

References 47 publications

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“…In fact, the role of type I IFNs in bacterial diseases is controversial, and most studies have focused on intracellular bacteria. Signaling through the type I IFN pathway can have harmful effects in some bacterial infections and beneficial consequences in others (55,(58)(59)(60)(61)(62).…”

Section: Discussionmentioning

confidence: 99%

Exacerbated Type II Interferon Response Drives Hypervirulence and Toxic Shock by an Emergent Epidemic Strain of Streptococcus suis

et al. 2013

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b Streptococcus suis, a major porcine pathogen, can be transmitted to humans and cause severe symptoms. A large human outbreak associated with an unusual streptococcal toxic shock-like syndrome (STSLS) was described in China. Albeit an early burst of proinflammatory cytokines following Chinese S. suis infection was suggested to be responsible for STSLS case severity, the mechanisms involved are still poorly understood. Using a mouse model, the host response to S. suis infection with a North American intermediately pathogenic strain, a European highly pathogenic strain, and the Chinese epidemic strain was investigated by a whole-genome microarray approach. Proinflammatory genes were expressed at higher levels in mice infected with the Chinese strain than those infected with the European strain. The Chinese strain induced a fast and strong gamma interferon (IFN-␥) response by natural killer (NK) cells. In fact, IFN-␥-knockout mice infected with the Chinese strain showed significantly better survival than wild-type mice. Conversely, infection with the less virulent North American strain resulted in an IFN-␤-subjugated, low inflammatory response that might be beneficial for the host to clear the infection. Overall, our data suggest that a highly virulent epidemic strain has evolved to massively activate IFN-␥ production, mainly by NK cells, leading to a rapid and lethal STSLS.

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Section: Discussionmentioning

confidence: 99%

Exacerbated Type II Interferon Response Drives Hypervirulence and Toxic Shock by an Emergent Epidemic Strain of Streptococcus suis

et al. 2013

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“…Tissues were harvested and processed as previously described (16). Briefly, mice were anesthetized with a lethal dose of tribromoethanol (240 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

“…Mice were exposed to aerosolized M. bovis BCG in an inhalation exposure system (Glas-Col, Terre Haute, IN) as previously described (16). Uninfected mice served as controls.…”

Section: Methodsmentioning

confidence: 99%

Modulation of Pulmonary Dendritic Cell Function during Mycobacterial Infection

et al. 2008

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We have previously reported that during mycobacterial infection, naïve CD4؉ T-cell activation is enhanced in the lungs. We investigated the role of chemokine receptor CCR7 and its ligands in the ability of CD11c؉ lung dendritic cells (DCs) to activate naïve CD4 ؉ T cells during pulmonary infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG). BCG infection resulted in the accumulation and maturation in the lungs of DCs that persisted as the mycobacterial burden declined. Lung DCs from infected mice expressed more major histocompatibility complex class II (MHC-II) than those from uninfected mice. CCR7 expression levels on lung DCs were comparable among uninfected and infected mice. The gene expression of the CCR7 ligand CCL19 progressively increased throughout BCG infection, and its expression was MyD88 dependent. CD11c؉ lung cells from BCG-infected mice activated ovalbumin (OVA)-specific naïve CD4؉ T cells more than CD11c ؉ lung cells from uninfected mice. Interestingly, during peak mycobacterial infection, CD11c hi MHC hi lung DCs had slightly decreased chemotaxis toward the CCR7 ligand CCL21 and less efficiency in activating naive CD4 ؉ T cells than DCs from mice during late-stage infection, when few bacilli are found in the lung. These findings suggest that during BCG infection, the inflammation and sustained expression of CCL19 result in the recruitment, activation, and retention in the lung of DCs that can activate naïve CD4 ؉ T cells in situ.During pulmonary mycobacterial infection, the migration of dendritic cells (DCs) and the dissemination of mycobacteria to draining lymph nodes are thought to be important for a successful cell-mediated immune response (6,22,36). Upon the engagement of Toll-like receptors (TLRs) on DCs by mycobacterium-derived, pathogen-associated molecular patterns, DCs undergo a coordinated maturation program that upregulates expression of the chemokine receptor CCR7. Chemokine receptor CCR7 expression is essential for the migration of DCs to the lymph nodes, where they coordinate adaptive immune responses following TLR stimulation (9,17,23,33,34).CCR7 and its ligands, CCL19 (Epstein-Barr virus-induced molecule 1 ligand chemokine) and CCL21 (secondary lymphoid chemokine), are important for both the initiation and regulation of adaptive immunity, as they direct the migration of mature DCs, naïve CD4 ϩ T cells, and central memory T cells to secondary lymphoid organs (SLOs) (31, 32). There are two isoforms of CCL21: CCL21-ser and CCL21-leu. CCL19 and CCL21-ser are produced by stromal cells within the T-cell zones of SLOs. CCL21-ser is also expressed in high endothelial venules, while CCL21-leu is expressed only in the lymphatic endothelium. Upon maturation, DCs also express CCL19 (26). Both CCL19 and CCL21 are involved in the organization of lymphoid structures under normal and chronic inflammatory conditions by facilitating encounters among stromal cells, T cells, B cells, and DCs (1,20,21).CCR7 may have a restricted role in immune responses to airborne pathogens. Mice lackin...

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“…Studies on Legionella pneumonphila (11), Salmonella typhimurium (12), Shigella flexneri (13), Bacillus anthrasis (14) and Mycobacterium bovis bacillus Calmette-Guérin (15) showed that IFNIs are protective for host, at least partially through enhancing IFN-␥/NO production and suppressing bacterial invasion. In contrast, some studies have shown that IFNIs are detrimental, especially in certain bacterial infections.…”

Section: T He Group Of Type I Ifns (Ifnis)mentioning

confidence: 99%

Type I IFNs Enhance Susceptibility toChlamydia muridarumLung Infection by Enhancing Apoptosis of Local Macrophages

Qiu

Fan

Joyee

et al. 2008

The Journal of Immunology

109

110

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Type I IFNs (IFNIs) have pleiotropic functions in regulating host innate and adaptive immune responses to pathogens. To elucidate the role of IFNIs in host resistance to chlamydial infection in vivo, we compared IFN-α/β receptor knockout (IFNAR−/−) and wild-type control mice in susceptibility to Chlamydia trachomatis mouse pneumonitis (Chlamydia muridarum) lung infection. We found that the IFNAR−/− mice were significantly more resistant to C. muridarum infection showing less bacterial burden and bodyweight loss, and milder pathological changes. However, IFN-γ response, which is believed to be critical in host defense against chlamydial infection, was similar between the wild-type and IFNAR−/− mice. More importantly, TUNEL analysis showed less macrophage apoptosis in IFNAR−/− mice, which was consistent with lower expressions of IFNI-induced apoptotic factors, TRAIL, Daxx, and PKR. Furthermore, depletion of lung macrophages with dichloromethylene diphosphonate-liposome significantly increased the susceptibility of the IFNAR−/− mice to C. muridarum, confirming the importance of macrophages. Overall, the data indicate that IFNIs play a promoting role in C. muridarum lung infection, largely through increase of local macrophage apoptosis.

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Interferon‐αβ mediates partial control of early pulmonary Mycobacterium bovis bacillus Calmette–Guérin infection

Cited by 35 publications

References 47 publications

Exacerbated Type II Interferon Response Drives Hypervirulence and Toxic Shock by an Emergent Epidemic Strain of Streptococcus suis

Exacerbated Type II Interferon Response Drives Hypervirulence and Toxic Shock by an Emergent Epidemic Strain of Streptococcus suis

Modulation of Pulmonary Dendritic Cell Function during Mycobacterial Infection

Type I IFNs Enhance Susceptibility toChlamydia muridarumLung Infection by Enhancing Apoptosis of Local Macrophages

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