Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice

Robbins, Clinton S.; Bauer, Carla M. T.; Vujicić, N; Gaschler, Gordon J.; Lichty, Brian D.; Brown, Earl G.; Stämpfli, Martin R.

doi:10.1164/rccm.200604-561oc

Cited by 92 publications

(93 citation statements)

References 57 publications

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“…Pertinent to NSCLC patients is the fact that CD8þ T-cell predominance is a characteristic of smoking-related chronic obstructive pulmonary disease (11), and it is thought to drive the progression of emphysema (12). In mouse models, activation of CD8þ T cells is impaired in the presence of cigarette smoke (13,14), perhaps explaining this finding in NSCLC patients. In fact, studies that report correlation between CD8þ TILs and prognosis contradict each other (15,16).…”

Section: Tumor-infiltrating Lymphocytesmentioning

confidence: 99%

Prognostic Immune Markers in Non–Small Cell Lung Cancer

Suzuki

Kachala

Kadota

et al. 2011

Clinical Cancer Research

151

104

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Tumor-associated immune responses have polarized effects in regulating tumor growth. Although a clear association has been shown between the tumor immune response and clinical outcome in colorectal and ovarian cancers, the role of immune markers for stratifying prognosis in non-small cell lung cancer (NSCLC) is less defined. Herein, we review the prognostic significance of published immune markers in the tumor microenvironment and peripheral blood of NSCLC patients. To identify prognostic immune genes, we reviewed all published gene-profiling studies in NSCLC and delineated the significance of immune genes by doing subanalysis on the microarray database of the NIH Director's Challenge study. This first comprehensive review of prognostic immune markers provides a foundation for further investigating immune responses in NSCLC.

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Section: Tumor-infiltrating Lymphocytesmentioning

confidence: 99%

Prognostic Immune Markers in Non–Small Cell Lung Cancer

Suzuki

Kachala

Kadota

et al. 2011

Clinical Cancer Research

151

104

View full text Add to dashboard Cite

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“…NTHi-specific antibodies were detected in the BALF or serum using a minor modification of the procedure previously described [23]. Briefly, MaxiSorp plates (Nalgene Nunc International, Mississauga, ON, Canada) were coated overnight at 4uC with a lysate from logarithmic-phase NTHi.…”

Section: Preparation Of Nthimentioning

confidence: 99%

Mechanisms of clearance of nontypeableHaemophilus influenzaefrom cigarette smoke-exposed mouse lungs

Gaschler¹,

Zavitz²,

Bauer³

et al. 2010

Eur Respir J

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Inflammation is prevalent in all stages of chronic obstructive pulmonary disease, and, furthermore, individuals undergo periods of exacerbation, during which pulmonary inflammation increases, often a result of bacterial infection. The present study investigates the in vivo consequences of cigarette smoke exposure on bacterial challenge with nontypeable Haemophilus influenzae (NTHi).BALB/c and C57 black 6 (C57BL/6) mice were exposed to cigarette smoke once or twice daily for a total period of 8 weeks.Exacerbated inflammation was observed in cigarette smoke-exposed compared to room-airexposed mice following challenge with live or heat-inactivated NTHi. Accelerated clearance of live NTHi from cigarette smoke-exposed mice was independent of the establishment of chronic inflammation or direct toxic effects of cigarette smoke components on bacteria. Mechanistically, a cell-free factor in the bronchoalveolar lavage fluid contributed to accelerated clearance following passive transfer to naive mice. Further investigation demonstrated increased titres of immunoglobulin A in the bronchoalveolar lavage fluid, but not the blood, of cigarette smoke-exposed mice, including increased titres of NTHi-specific immunoglobulin A, whereas heavy chain joining element (J H ) -/-B-cell-deficient cigarette smoke-exposed mice did not demonstrate decreased bacterial burden following challenge. The present results demonstrate that cigarette smoke exposure results in exacerbated inflammation following challenge with NTHi, as well as increased titres of antibodies that contribute to bacterial clearance.

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“…IFN bioactivity was measured in BAL samples by plaque reduction assay as described previously (31). Briefly, BAL samples were assessed for their ability to protect primary IFN regulatory factor-3-deficient mouse embryonic fibroblasts (MEFs) (provided by Dr. K. Mossman, McMaster University, Hamilton, Ontario, Canada) from infection with a vesicular stomatitis virus expressing GFP under an endogenous viral promoter (VSV-GFP; provided by Dr. B. Lichty, McMaster University).…”

Section: Measurement Of Type I Ifn By Plaque Reduction Assaymentioning

confidence: 99%

“…Influenza-and B. parapertussis-specific Abs were detected in the BAL or serum using a minor modification of the procedure described previously (31). Briefly, MaxiSorp plates (Nalge Nunc International, Rochester, NY) were coated overnight at 4˚C with a lysate from influenza-infected HELA cells or with a lysate from log-phase B. parapertussis bacteria.…”

Section: Ag-specific Ig Elisamentioning

confidence: 99%

Dysregulated Macrophage-Inflammatory Protein-2 Expression Drives Illness in Bacterial Superinfection of Influenza

Zavitz¹,

Bauer²,

Gaschler³

et al. 2010

The Journal of Immunology

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Influenza virus infection is a leading cause of death and disability throughout the world. Influenza-infected hosts are vulnerable to secondary bacterial infection, however, and an ensuing bacterial pneumonia is actually the predominant cause of influenza-attributed deaths during pandemics. A number of mechanisms have been proposed by which influenza may predispose to superinfection with an unrelated or heterologous pathogen, but the subsequent interaction between the host, virus, and bacteria remains an understudied area. In this study, we develop and examine a novel model of heterologous pulmonary infection in which an otherwise subclinical Bordetella parapertussis infection synergizes with an influenza virus infection to yield a life-threatening secondary pneumonia. Despite a profound pulmonary inflammatory response and unaltered viral clearance, bacterial clearance was significantly impaired in heterologously infected mice. No deficits were observed in pulmonary or systemic adaptive immune responses or the viability or function of infiltrating inflammatory cells to explain this phenomenon, and we provide evidence that the onset of severe pulmonary inflammation actually precedes the increased bacterial burden, suggesting that exacerbated inflammation is independent of bacterial burden. To that end, neutralization of the ELR+ inflammatory chemokine MIP-2 (CXCL2/GRO-β) attenuated the inflammation, weight loss, and clinical presentation of heterologously infected mice without impacting bacterial burden. These data suggest that pulmonary inflammation, rather than pathogen burden, is the key threat during bacterial superinfection of influenza and that selective chemokine antagonists may be a novel therapeutic intervention in cases of bacterial superinfection of influenza.

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Cigarette Smoke Impacts Immune Inflammatory Responses to Influenza in Mice

Abstract: Our study suggests that, in mice, cigarette smoke affects primary antiviral immune-inflammatory responses, whereas secondary immune protection remains intact.

Cited by 92 publications

References 57 publications

Prognostic Immune Markers in Non–Small Cell Lung Cancer

Prognostic Immune Markers in Non–Small Cell Lung Cancer

Mechanisms of clearance of nontypeableHaemophilus influenzaefrom cigarette smoke-exposed mouse lungs

Dysregulated Macrophage-Inflammatory Protein-2 Expression Drives Illness in Bacterial Superinfection of Influenza

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