Local CD11c+ MHC Class II− Precursors Generate Lung Dendritic Cells during Respiratory Viral Infection, but Are Depleted in the Process

Wang, Hongwei; Peters, N.; Laza-Stanca, Vasile; Nawroly, Niga; Johnston, Sebastian L.; Schwarze, Jürgen

doi:10.4049/jimmunol.177.4.2536

Cited by 43 publications

(43 citation statements)

References 33 publications

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“…3c). This finding, although similar to what has been reported by at least one other group, contrasts with reports suggesting that lung cDCs were of the myeloid (CD11b ϩ ) phenotype at baseline (22,29,30). With viral inoculation, we found expression of CD11b as well as the costimulatory molecule CD86 and increased expression of MHC-II (Fig.…”

Section: Paramyxoviral Respiratory Infection Alters Lung DC Levelscontrasting

confidence: 57%

“…Previous work on respiratory viral disease and lung DCs has focused primarily on RSV infection of BALB/c mice (15,16,22,23). In this RSV model, the number of both cDCs and pDCs appear to increase in the airway tissue with viral infection.…”

Section: Discussionmentioning

confidence: 99%

“…RSV would have been a useful choice for study because it is the most common cause of serious respiratory illness in early childhood and is most often associated with the development of childhood asthma. Indeed, several previous studies examined the DC response to RSV in mice (15,16,22,23). Unfortunately, mice are relatively resistant to infection with RSV; therefore, a high threshold inoculum of virus must be given and the resulting all-or-none pattern of illness manifests primarily as alveolitis with viral localization to type I alveolar epithelial cells (Ref.…”

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confidence: 99%

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Controls for Lung Dendritic Cell Maturation and Migration during Respiratory Viral Infection

Grayson

Ramos

Rohlfing

et al. 2007

The Journal of Immunology

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Dendritic cells are ideally suited to orchestrate the innate and adaptive immune responses to infection, but we know little about how these cells respond to infection with common respiratory viruses. Paramyxoviral infections are the most frequent cause of serious respiratory illness in childhood and are associated with an increased risk of asthma. We therefore used a high-fidelity mouse model of paramyxoviral respiratory infection triggered by Sendai virus to examine the response of conventional and plasmacytoid dendritic cells (cDCs and pDCs, respectively) in the lung. We found that pDCs are scarce at baseline but become the predominant population of lung dendritic cells during infection. This recruitment allows for a source of IFN-α locally at the site of infection. In contrast, cDCs rapidly differentiate into myeloid cDCs and begin to migrate from the lung to draining lymph nodes within 2 h after viral inoculation. These events cause the number of lung cDCs to decrease rapidly and remain decreased at the site of viral infection. Maturation and migration of lung cDCs depends on Ccl5 and Ccr5 signals because these events are significantly impaired in Ccl5−/− and Ccr5−/− mice. cDCs failure to migrate to draining lymph nodes in Ccl5−/− or Ccr5−/− mice is associated with impaired up-regulation of CCR7 that would normally direct this process. Our results indicate that pDCs and cDCs respond distinctly to respiratory paramyxoviral infection with patterns of movement that should serve to coordinate the innate and adaptive immune responses, respectively.

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Section: Paramyxoviral Respiratory Infection Alters Lung DC Levelscontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Controls for Lung Dendritic Cell Maturation and Migration during Respiratory Viral Infection

Grayson

Ramos

Rohlfing

et al. 2007

The Journal of Immunology

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“…As has been shown in murine models of respiratory viral infection, potent type I IFN stimulation causes significant loss of CD11c + cells from the lung and appears to have an important role in immunoregulation in the airways (32,33). The WT mice had significantly more TNF-α in their airways than Ifnar -/-mice, and we have previously demonstrated that TNF-α signaling is associated with substantial pulmonary pathology in response to S. aureus (7).…”

Section: Discussionmentioning

confidence: 91%

Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A

Martin¹,

Gómez²,

Wetzel³

et al. 2009

J. Clin. Invest.

104

115

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The activation of type I IFN signaling is a major component of host defense against viral infection, but it is not typically associated with immune responses to extracellular bacterial pathogens. Using mouse and human airway epithelial cells, we have demonstrated that Staphylococcus aureus activates type I IFN signaling, which contributes to its virulence as a respiratory pathogen. This response was dependent on the expression of protein A and, more specifically, the Xr domain, a short sequence-repeat region encoded by DNA that consists of repeated 24-bp sequences that are the basis of an internationally used epidemiological typing scheme. Protein A was endocytosed by airway epithelial cells and subsequently induced IFN-β expression, JAK-STAT signaling, and IL-6 production. Mice lacking IFN-α/β receptor 1 (IFNAR-deficient mice), which are incapable of responding to type I IFNs, were substantially protected against lethal S. aureus pneumonia compared with wild-type control mice. The profound immunological consequences of IFN-β signaling, particularly in the lung, may help to explain the conservation of multiple copies of the Xr domain of protein A in S. aureus strains and the importance of protein A as a virulence factor in the pathogenesis of staphylococcal pneumonia.

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“…In recent years, it has become evident that BM DC precursors enter the circulation and extravasate into secondary lymphoid organs, skin, and lung where they finally differentiate into DCs. 18,19,21,22,[24][25][26][27][28] In the steady state, spleen and lymph node DCs do not seem to be derived from monocytes but from specialized precursors. 21,29 Regulation of cellular homeostasis in other immune compartments is relatively well defined.…”

mentioning

confidence: 99%

Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop

Hochweller

Miloud

Striegler

et al. 2009

Blood

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IntroductionDendritic cells (DCs) are rare immune cells scattered in lymphoid and nonlymphoid organs throughout the body serving as pivotal coordinators of the immune system. 1,2 A key feature of DCs is that they set a fine balance between protective and pathologic immune responses. On the one hand, DCs are required to generate immunity against invading pathogens 3-7 and T-cell tolerance to self, 1,[8][9][10] depending on their activation status. On the other hand, a relatively small increase in DC numbers results in T-cell hyperactivation and autoimmunity. 11,12 Thus, it is crucial to maintain an optimal number of DCs whereby both T-cell immunity and tolerance are achieved. Despite the critical function of DCs in regulating innate and adaptive immune response, 1-7 very little is known about the homeostatic control of DC numbers.In addition, lineage commitment and differentiation of DC precursors are only beginning to be understood. [13][14][15][16] As hematopoietic cells, DCs originate from myeloid precursors (MPs) in bone marrow (BM). 17 A common macrophage and DC precursor (MDP) has been identified in BM. 18 Specialized precursors with the capacity to differentiate exclusively into DCs have also been identified such as the common DC precursor (CDP) 19 and pro-DC 20 in BM, and the immediate pre-DC precursor in BM, spleen, and lymph nodes. [20][21][22] Recently, a linear differentiation from MPs to MDPs, CDPs, pre-DCs, and DCs has been suggested. 23 Pro-DCs and CDPs in the BM share phenotypical characteristics 19,20 and both differentiate into pre-DCs, 19,20,23 but whether they represent the same cell population remains to be formally elucidated. In recent years, it has become evident that BM DC precursors enter the circulation and extravasate into secondary lymphoid organs, skin, and lung where they finally differentiate into DCs. 18,19,21,22,[24][25][26][27][28] In the steady state, spleen and lymph node DCs do not seem to be derived from monocytes but from specialized precursors. 21,29 Regulation of cellular homeostasis in other immune compartments is relatively well defined. For example, the size of the lymphocyte compartment is mainly controlled by the proliferation of mature T and B cells in the periphery, where competition for growth factors, such as IL-7, and MHC recognition by T cells dictates the extent of cell division. [30][31][32][33][34] In contrast to lymphocytes, homeostasis of neutrophils is partly achieved by the regulated release of neutrophils from the BM via GM-CSF, CXCR4, and SDF-1. 35,36 Regarding the DC compartment, Flt3 ligand (Flt3-L) is known to be required for its generation 37 by promoting proliferation and differentiation of DC precursors. 17,26 However, it is not known whether the maintenance of DC numbers in lymphoid organs during noninfectious states is the result of a passive or active process. The former implies that a steady rate of generation from precursors equals the rate of DC death, resulting in a constant size of the DC compartment (eg, 3 ϫ 10 6 DCs per mouse spleen). I...

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Local CD11c+ MHC Class II− Precursors Generate Lung Dendritic Cells during Respiratory Viral Infection, but Are Depleted in the Process

Cited by 43 publications

References 33 publications

Controls for Lung Dendritic Cell Maturation and Migration during Respiratory Viral Infection

Controls for Lung Dendritic Cell Maturation and Migration during Respiratory Viral Infection

Staphylococcus aureus activates type I IFN signaling in mice and humans through the Xr repeated sequences of protein A

Homeostasis of dendritic cells in lymphoid organs is controlled by regulation of their precursors via a feedback loop

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