Susceptibility of Prostate Epithelial Cells to<i>Chlamydia muridarum</i>Infection and Their Role in Innate Immunity by Recruitment of Intracellular Toll-Like Receptors 4 and 2 and MyD88 to the Inclusion

Mackern-Oberti, Juan Pablo; Maccioni, Mariana; Cuffini, Cecilia; Gatti, Gerardo; Rivero, Virginia

doi:10.1128/iai.00593-06

Cited by 42 publications

(34 citation statements)

References 48 publications

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“…As is known, clathrin-dependent endocytosis is essential for viral internalization and intracellular processing and downstream inflammatory responses/signaling cascades (33). After internalization, viral particles enter the early endosomes, followed by trafficking into late endosomes/lysosomes for degradation or releasing to the cytoplasm to evade the lysosome degradation (42).…”

Section: Discussionmentioning

confidence: 99%

Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways

Pan

Zhang

Luo

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Since avian influenza virus H5N1-induced hypercytokemia plays a key role in acute lung injury, understanding its molecular mechanism is highly desirable for discovering therapeutic targets against H5N1 infection. In the present study, we investigated the role of autophagy in H5N1-induced lung inflammation by using H5N1 pseudotyped viral particles (H5N1pps). The results showed that H5N1pps significantly induced autophagy both in A549 human lung epithelial cells and in mouse lung tissues, which was primarily due to hemagglutinin (HA) of H5N1 virus. Blocking autophagy with 3-methyladenine (an autophagy inhibitor) or siRNA knockdown of autophagy-related genes (beclin1 and atg5) dramatically attenuated H5N1pp-induced proinflammatory cytokines and chemokines, such as IL-1␤, TNF-␣, IL-6, CCL2, and CCL5, both in vitro and in vivo. Autophagy-mediated inflammatory responses involved the activation of NF-B and p38 MAPK signaling pathways, which required the presence of clathrin but did not rely on p62 or autophagosome-lysosome fusion. On the other hand, the activation of NF-B also promoted H5N1pp-induced autophagosome formation. These data indicated a positive feedback loop between autophagy and NF-B signaling cascade, which could exacerbate H5N1pp-induced lung inflammation. Our data demonstrated an essential role of autophagy in H5N1pp-triggered inflammatory responses, and targeting the autophagic pathway could be a promising strategy to treat H5N1 virus-caused lung inflammation. avian influenza H5N1 virus; autophagy; lung inflammation; NF-B; p38 MAPK

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Section: Discussionmentioning

confidence: 99%

Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways

Pan

Zhang

Luo

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…TLR2 appears to be the predominant receptor required for an inflammatory response to infection (Prebeck et al 2001;Darville et al 2003;O'Connell et al 2006). Interestingly, TLR2 and its adaptor MyD88 localize to the periphery of the chlamydial inclusion during active infection, suggesting that TLR2 may signal intracellularly during infection (Mackern-Oberti et al 2006;O'Connell et al 2006).…”

Section: Modifying the Host Response Detection Of Chlamydia By The Hostmentioning

confidence: 99%

Chlamydial Intracellular Survival Strategies

Bastidas

Elwell

Engel

et al. 2013

Cold Spring Harbor Perspectives in Medicine

206

197

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Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and the causative agent of blinding trachoma. Although Chlamydia is protected from humoral immune responses by residing within remodeled intracellular vacuoles, it still must contend with multilayered intracellular innate immune defenses deployed by its host while scavenging for nutrients. Here we provide an overview of Chlamydia biology and highlight recent findings detailing how this vacuole-bound pathogen manipulates host -cellular functions to invade host cells and maintain a replicative niche.

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“…Second, C. trachomatis-induced cytokine production is largely dependent on MyD88 (35). Third, both TLRs and MyD88 can be recruited to the inclusion in the infected cells (36,37). Finally, mice deficient in TLR2 cleared infection as efficiently as wild-type mice but developed less pathology in the oviduct than the wild-type mice (38), whereas there was a slight increase in recovery of live organisms from vaginal samples of MyD88 KO mice (35).…”

mentioning

confidence: 99%

Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection

Chen

Lei

Chang

et al. 2010

The Journal of Immunology

110

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MyD88, a key adaptor molecule required for many innate immunity receptor-activated signaling pathways, was evaluated in a Chlamydia muridarum urogenital tract infection model. Compared with wild-type mice, MyD88 knockout (KO) mice failed to produce significant levels of inflammatory cytokines in the genital tract during the first week of chlamydial infection. MyD88 KO mice developed a Th2-dominant whereas wild-type mice developed a Th1/Th17-dominant immune response after chlamydial infection. Despite the insufficient production of early inflammatory cytokines and lack of Th1/Th17-dominant adaptive immunity, MyD88 KO mice appeared to be as resistant to chlamydial intravaginal infection as wild-type mice based on the number of live organisms recovered from vaginal samples. However, significantly high numbers of chlamydial organisms were detected in the upper genital tract tissues of MyD88 KO mice. Consequently, MyD88 KO mice developed more severe pathology in the upper genital tract. These results together have demonstrated that MyD88-dependent signaling pathway is not only required for inflammatory cytokine production in the early phase of host response to chlamydial infection but also plays a critical role in the development of Th1/Th17 adaptive immunity, both of which may be essential for limiting ascending infection and reducing pathology of the upper genital tract by chlamydial organisms.

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Susceptibility of Prostate Epithelial Cells toChlamydia muridarumInfection and Their Role in Innate Immunity by Recruitment of Intracellular Toll-Like Receptors 4 and 2 and MyD88 to the Inclusion

Cited by 42 publications

References 48 publications

Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways

Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways

Chlamydial Intracellular Survival Strategies

Mice Deficient in MyD88 Develop a Th2-Dominant Response and Severe Pathology in the Upper Genital Tract following Chlamydia muridarum Infection

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