Innate Immune Responses of Pulmonary Epithelial Cells to Burkholderia pseudomallei Infection

Sim, Siew Hoon; Liu, Yichun; Wang, Dongling; Novem, Vidhya; Sivalingam, Suppiah Paramalingam; Thong, Tuck Weng; Ooi, Eng Eong; Tan, Gladys

doi:10.1371/journal.pone.0007308

Cited by 29 publications

(40 citation statements)

References 46 publications

(53 reference statements)

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“…Since pangolins may have intrinsically weak mucosal immunity, Burkholderia spp. might easily infect the lung by penetrating lung epithelial cells and the brain by penetrating nasal mucosa and migrating to the brain through olfactory nerves, which has previously been shown with other Burkholderia (Owen et al 2009;Sim et al 2009;Taylor et al 2010;Dando et al 2014;St John et al 2014). Furthermore, captive pangolins are prone to frequently fatal gastrointestinal disease, pneumonia, and skin maladies (Clark et al 2008;Hua et al 2015).…”

Section: Discussionmentioning

confidence: 91%

Pangolin genomes and the evolution of mammalian scales and immunity

et al. 2016

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Pangolins, unique mammals with scales over most of their body, no teeth, poor vision, and an acute olfactory system, comprise the only placental order (Pholidota) without a whole-genome map. To investigate pangolin biology and evolution, we developed genome assemblies of the Malayan (Manis javanica) and Chinese (M. pentadactyla) pangolins. Strikingly, we found that interferon epsilon (IFNE), exclusively expressed in epithelial cells and important in skin and mucosal immunity, is pseudogenized in all African and Asian pangolin species that we examined, perhaps impacting resistance to infection. We propose that scale development was an innovation that provided protection against injuries or stress and reduced pangolin vulnerability to infection. Further evidence of specialized adaptations was evident from positively selected genes involving immunity-related pathways, inflammation, energy storage and metabolism, muscular and nervous systems, and scale/hair development. Olfactory receptor gene families are significantly expanded in pangolins, reflecting their well-developed olfaction system. This study provides insights into mammalian adaptation and functional diversification, new research tools and questions, and perhaps a new natural IFNE-deficient animal model for studying mammalian immunity.

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Section: Discussionmentioning

confidence: 91%

Pangolin genomes and the evolution of mammalian scales and immunity

et al. 2016

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“…Thus it is reasonable to conclude that as multiple TLRs are subject to stimulation by BP , but not BM , this likely contributed to the vigorous innate immune responses (e.g., cytokine secretion) induced by macrophages and ATII cells in the early stages of infection. Sim et al (2009) showed that primary murine epithelial lung cells both in vitro and in vivo secrete significant levels of pro-inflammatory cytokines in response to BP . Our findings, as well as others (Stevens and Galyov, 2004; Sim et al, 2009), resemble the clinical situation of acute melioidosis in that this disease can lead to induction of pro-inflammatory cytokines with high levels of cytokine secretion, leading to poorer prognosis for infected patients (Simpson et al, 2000; Cheng et al, 2007; Wiersinga et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Sim et al (2009) showed that primary murine epithelial lung cells both in vitro and in vivo secrete significant levels of pro-inflammatory cytokines in response to BP . Our findings, as well as others (Stevens and Galyov, 2004; Sim et al, 2009), resemble the clinical situation of acute melioidosis in that this disease can lead to induction of pro-inflammatory cytokines with high levels of cytokine secretion, leading to poorer prognosis for infected patients (Simpson et al, 2000; Cheng et al, 2007; Wiersinga et al, 2007). Alternatively, and very interestingly, BM stimulated minimal cytokine secretion from macrophages and ATII cells in the initial infection stage but stimulated the secretion of pro-inflammatory suppressor, IL-10.…”

Section: Discussionmentioning

confidence: 99%

“…While both BP and BM have been shown to readily adhere and invade transformed human and murine macrophage-like cell lines (Jones et al, 1996; Stevens and Galyov, 2004; Pudla et al, 2011) and ATII cell lines (Kespichayawattana et al, 2004; Utaisincharoen et al, 2004, 2005; Boddey et al, 2006; Sim et al, 2009; Whitlock et al, 2009; Balder et al, 2010), relatively few studies have examined the immunological outcomes-induced following infection of primary human cells (Nathan and Puthucheary, 2005; Puthucheary and Nathan, 2006) or performed direct comparisons of their differential infectivity process. This is likely due to the level 3 bio-containment facilities necessary to perform experiments with BM and BP .…”

Section: Introductionmentioning

confidence: 99%

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Burkholderia mallei and Burkholderia pseudomallei stimulate differential inflammatory responses from human alveolar type II cells (ATII) and macrophages

Lu¹,

Popov²,

Patel³

et al. 2012

Front. Cell. Inf. Microbio.

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Alveolar type II pneumocytes (ATII) and alveolar macrophages (AM) play a crucial role in the lung's innate immune response. Burkholderia pseudomallei (BP) and Burkholderia mallei (BM) are facultative Gram-negative bacilli that cause melioidosis and glanders, respectively. The inhalation of these pathogens can cause lethal disease and death in humans. We sought to compare the pathogenesis of and host responses to BP and BM through contact with human primary ATII cells and monocytes-derived macrophages (MDM). We hypothesized that because BP and BM induce different disease outcomes, each pathogen would induce distinct, unique host immune responses from resident pulmonary cells. Our findings showed that BP adhered readily to ATII cells compared to BM. BP, but not BM, was rapidly internalized by macrophages where it replicated to high numbers. Further, BP-induced significantly higher levels of pro-inflammatory cytokine secretion from ATII cells (IL-6, IL-8) and macrophages (IL-6, TNFα) at 6 h post-infection compared to BM (p < 0.05). Interestingly, BM-induced the anti-inflammatory cytokine, IL-10, in ATII cells and macrophages at 6 h post-infection, with delayed induction of inflammatory cytokines at 24 h post-infection. Because BP is flagellated and produces LPS, we confirmed that it stimulated both Toll-like receptor (TLR) 4 and TLR5 via NF-κb activation while the non-flagellated BM stimulated only TLR4. These data show the differences in BP and BM pathogenicity in the lung when infecting human ATII cells and macrophages and demonstrate the ability of these pathogens to elicit distinct immune responses from resident lung cells which may open new targets for therapeutic intervention to fight against these pathogens.

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“…Isolation of normal lung cells from mice was done as previously described (18,19). Lung tissue was separated and flushed with 10 mL of 1% of penicillin-streptomycin in PBS.…”

Section: Preparation Of Normal Lung Cells From Mousementioning

confidence: 99%

Cancer-Targeted BikDD Gene Therapy Elicits Protective Antitumor Immunity against Lung Cancer

Sher

Liu

Chang

et al. 2011

Molecular Cancer Therapeutics

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Targeted cancer-specific gene therapy is a promising strategy for treating metastatic lung cancer, which is a leading cause of lung cancer-related deaths. Previously, we developed a cancer-targeted gene therapy expression system with high tumor specificity and strong activity that selectively induced lung cancer cell killing without affecting normal cells in immunocompromised mice. Here, we found this cancer-targeted gene therapy, SV-BikDD, composed of the survivin promoter in the VP16-GAL4-WPRE integrated systemic amplifier system to drive the apoptotic gene BikDD, not only caused cytotoxic effects in cancer cells but also elicited a cancer-specific cytotoxic T lymphocyte response to synergistically increase the therapeutic effect and further develop an effective systemic antitumoral immunity against rechallenges of

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Innate Immune Responses of Pulmonary Epithelial Cells to Burkholderia pseudomallei Infection

Cited by 29 publications

References 46 publications

Pangolin genomes and the evolution of mammalian scales and immunity

Pangolin genomes and the evolution of mammalian scales and immunity

Burkholderia mallei and Burkholderia pseudomallei stimulate differential inflammatory responses from human alveolar type II cells (ATII) and macrophages

Cancer-Targeted BikDD Gene Therapy Elicits Protective Antitumor Immunity against Lung Cancer

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