Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells

Dahl, Martin E.; Dabbagh, Karim; Liggitt, Denny; Kim, Sung Hoon; Lewis, David B.

doi:10.1038/ni1041

Cited by 193 publications

(168 citation statements)

References 49 publications

Supporting

Mentioning

145

Contrasting

Unclassified

Order By: Relevance

“…S1). Using the influenza model, Dahl et al (16) reported that lung DCs from recovered mice display sustained, increased levels of costimulatory markers. Given that DC activation has the potential to impair antigen presentation (18), this could explain the failure to detect evidence of pMHCI expression beyond 1 week or so after infectious virus clearance ( Figs.…”

Section: Pulmonary DC Status In Naïve and Previously Infected Hostsmentioning

confidence: 99%

See 1 more Smart Citation

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection

Mintern

Bedoui²,

Davey³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Antigen expressed as MHC Class I glycoprotein (pMHCI) complexes on dendritic cells is the primary driver of CD8 ؉ T cell clonal expansion and differentiation. As we seek to define the molecular differences between acutely stimulated cytotoxic T lymphocyte (CTL) effectors and long-lived memory T cells, it is essential that we understand the duration of in vivo pMHCI persistence. Although infectious influenza A virus is readily cleared by mammalian hosts, that does not necessarily mean that all influenza antigen is totally eliminated. An exhaustive series of carefully controlled adoptive transfer experiments using 3 different carboxy fluorescein diacetate succinimidyl esterlabeled T cell receptor-transgenic CTL populations and a spectrum of genetically engineered and wild-type influenza A viruses provided no evidence for pMHCI persistence over the 30 -60-d interval after virus challenge. Molecular profiles identified in antigen-specific T cells at this time may thus be considered to reflect established immunologic memory and not recent CTL activation from a persistent pMHCI pool. V irus-specific CD8ϩ T cell-mediated immunity is a critical component of the host response. Naive CD8 ϩ T cells recognize virus-derived peptides presented in the context of MHC Class I glycoproteins (pMHCI). Encountering these pMHCI complexes on professional antigen-presenting cells (APCs) in draining lymph nodes (1) triggers CD8 ϩ T cell proliferation and differentiation (2, 3) to mediate cytotoxic T lymphocyte (CTL) effector function, a primary mechanism of virus clearance (4). Other clonally expanded CD8 ϩ T cells survive to establish a stable memory pool (2). Although it is possible to probe the molecular events that underlie these events using in vitro culture systems, what happens to T cells during and after an infectious challenge is optimally determined by minimizing the extent of manipulation after lymphocyte separation from the intact host. For example, we have recently demonstrated that a minority of influenza-specific memory CTLs recovered directly ex vivo can maintain cytotoxic gene expression for up to 1 year after infection (5). Understanding what this means in a molecular sense requires a clear picture of the likely stimulatory environment. Defining the importance of antigen load through the establishment and maintenance phases of CD8ϩ T cell immunity is also essential if we are to take rational approaches to vaccine design.Some viruses that first establish an acute, lytic infectious process have evolved mechanisms that allow them to persist at a low level (or in a latent form) for the life of the host. This is not the case for influenza in immunologically competent mice or, so far as we are aware, in other mammalian species. Numerous lines of evidence based on (i) feeding the thymidine analogue bromodeoxyuridine to monitor antigen-specific T cell expansion (6), (ii) isolating dendritic cells (DCs) to probe for pMHCI expression (7), and (iii) PCR to detect viral genome in the recovered lung (8-10) support the view that the...

show abstract

Section: Pulmonary DC Status In Naïve and Previously Infected Hostsmentioning

confidence: 99%

“…1 and 2) could be thought to reflect that the APC environment is in some way compromised after the acute phase of this viral pneumonia is resolved (16,17). To exclude that possibility, we examined the status of the regional lymph node/pulmonary DC network.…”

Section: Pulmonary DC Status In Naïve and Previously Infected Hostsmentioning

confidence: 99%

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection

Mintern

Bedoui²,

Davey³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…[35][36][37][38] Moreover, recent studies demonstrated an inhibitory effect of parasitic infections on allergy/asthma. [27][28][29][30] However, this hypothesis currently faces numerous challenges, [39][40][41][42][43][44][45] because some epidemiological studies have been performed on populations with different genetic backgrounds, culture, economic development stage, health care system and geographical location, and they have shown either no relationship between infection and allergy, especially asthma, or an increased risk of allergic asthma in association with infection. [40][41][42][43][44][45][46] In experimental models, some infections, such as acute infections, exacerbated already established allergy/ asthma or enhanced allergic reactions when the allergen and infectious agents were co-administered.…”

Section: Introductionmentioning

confidence: 99%

Role of dendritic cells: a step forward for the hygiene hypothesis

Yang

Gao

2010

Cell Mol Immunol

View full text Add to dashboard Cite

The hygiene hypothesis was proposed more than two decades ago, but its mechanism remains unclear. This review focuses on recent advances in the field, especially on the role played by dendritic cells (DCs) and their modulating effects on various infections and allergic diseases, including allergic asthma. DCs isolated from mice long after the resolution of an infection were reported to have a significant modulating effect on allergen-specific Th2 responses in both in vitro and in vivo systems. These DCs showed DC1-like and/or tolerogenic DC capacity, which allowed for the inhibition of allergic responses by immune deviation (enhancing Th1 response) and immune regulation (through regulatory T-cell and Th2 hyporesponsiveness) mechanisms. These findings represented a significant advance in the elucidation of the mechanisms underlying the hygiene hypothesis. Further investigation on the mechanisms by which DCs are 'educated' by infectious agents and the influence of the type, time, and extent of infections on this 'education' process will help us understand immune regulation in disease settings and in the rational design of preventive/therapeutic approaches to allergy/asthma and infections.

show abstract

“…Interestingly, respiratory viral infections have been implicated in exacerbations of allergic asthma, characterized by a Th2-biased immune response (41). Contoli showed deficient induction of IFN by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers (42).…”

Section: Discussionmentioning

confidence: 99%

<i>Alternaria</i> Inhibits Double-stranded RNA-Induced Cytokines Productions through TLR3

et al. 2015

View full text Add to dashboard Cite

show abstract

Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells

Cited by 193 publications

References 49 publications

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection

Transience of MHC Class I-restricted antigen presentation after influenza A virus infection

Role of dendritic cells: a step forward for the hygiene hypothesis

<i>Alternaria</i> Inhibits Double-stranded RNA-Induced Cytokines Productions through TLR3

Contact Info

Product

Resources

About