Abstract：
:Neutrophils clear viruses, but excessive neutrophil responses induce tissue injury and worsen disease. Aging increases mortality to influenza infection; however, whether this is due to impaired viral clearance or a pathological host immune response is unknown. Here we show that aged mice have higher levels of lung neutrophils than younger mice after influenza viral infection. Depleting neutrophils after, but not before, infection substantially improves the survival of aged mice without altering viral clearance. Aged alveolar epithelial cells (AECs) have a higher frequency of senescence and secrete higher levels of the neutrophil-attracting chemokines CXCL1 and CXCL2 during influenza infection. These chemokines are required for age-enhanced neutrophil chemotaxis in vitro. Our work suggests that aging increases mortality from influenza in part because senescent AECs secrete more chemokines, leading to excessive neutrophil recruitment. Therapies that mitigate this pathological immune response in the elderly might improve outcomes of influenza and other respiratory infections.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
Kulkarni U,Zemans RL,Smith CA,Wood SC,Deng JC,Goldstein DRdoi
10.1038/s41385-018-0115-3subject
Has Abstractpub_date
2019-03-01 00:00:00pages
545-554issue
2eissn
1933-0219issn
1935-3456pii
10.1038/s41385-018-0115-3journal_volume
12pub_type
杂志文章abstract：:Induction of mucosal immunity is critical for protection from enteric pathogens. Heat shock protein gp96 is one of the primary peptide and protein chaperones located in the endoplasmic reticulum. We reported previously that a cell-secreted gp96-Ig fusion protein (gp96-Ig) mediated strong systemic, antigen-specific CD8...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2009.127
更新日期：2010-03-01 00:00:00
abstract：:Helminth infection leads to the local proliferation and accumulation of macrophages in tissues. However, the function of macrophages during helminth infection remains unclear. SH2-containing inositol 5'-phosphatase 1 (Ship1, Inpp5d) is a lipid phosphatase that has been shown to play a critical role in macrophage funct...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2012.29
更新日期：2012-09-01 00:00:00
abstract：:Malaria-associated acute respiratory distress syndrome (MA-ARDS) and acute lung injury (ALI) are complications that cause lung damage and often leads to death. The MA-ARDS/ALI is associated with a Type 1 inflammatory response mediated by T lymphocytes and IFN-γ. Here, we used the Plasmodium berghei NK65 (PbN)-induced ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-018-0093-5
更新日期：2019-03-01 00:00:00
abstract：:Colonization of the nasopharyngeal mucosa by meningococcus and other polysaccharide (PS)-encapsulated bacteria precedes invasion. PS-conjugate vaccines induce PS-specific B-cell memory (B(MEM)) and also prevent colonization, thus blocking person-to-person transmission, generating herd protection. However, in isolation...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2012.70
更新日期：2013-03-01 00:00:00
abstract：:Specific components of the intestinal microbiota are capable of influencing immune responses such that a mutualistic relationship is established. In mice, colonization with segmented filamentous bacteria (SFB) induces T-helper-17 (Th17) cell differentiation in the intestine, yet the effector functions of interleukin (...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2016.80
更新日期：2017-05-01 00:00:00
abstract：:IFN-γ is known as a pro-inflammatory cytokine, but can also block inflammation in certain chronic diseases although the underlying mechanisms are poorly understood. We found that IFN-γ rapidly induced Noxa expression and that extent of inflammation by repeated house dust mite exposure was enhanced in noxa-/- compared ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2017.117
更新日期：2018-05-01 00:00:00
abstract：:Cells of the mononuclear phagocyte system (MPS) are found in large numbers in every organ of the body, where they contribute to innate and acquired immunity and homeostasis. This review considers the locations of MPS cells, surface markers that distinguish subsets of monocytes and macrophages, the pathways of MPS diff...
journal_title：Mucosal immunology
pub_type： 杂志文章,评审
doi：10.1038/mi.2008.36
更新日期：2008-11-01 00:00:00
abstract：:The seasonal burden of influenza coupled with the pandemic outbreaks of more pathogenic strains underscore a critical need to understand the pathophysiology of influenza injury in the lung. Interleukin-22 (IL-22) is a promising cytokine that is critical in protecting the lung during infection. This cytokine is strongl...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0206-9
更新日期：2020-01-01 00:00:00
abstract：:The generation of tissue-resident memory T cells (TRM) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of TRM is one of the principal advantages of mucosally administered vaccines. We have previously shown that antigen-specific, IL-17-producing CD4+ T cell...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0218-5
更新日期：2020-01-01 00:00:00
abstract：:Chronic beryllium disease (CBD) is a granulomatous lung disorder that is associated with the accumulation of beryllium (Be)-specific CD4(+) T cells into the lung. Genetic susceptibility is linked to HLA-DPB1 alleles that possess a glutamic acid at position 69 (βGlu69), and HLA-DPB1*02:01 is the most prevalent βGlu69-c...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2015.54
更新日期：2016-01-01 00:00:00
abstract：:Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-018-0049-9
更新日期：2018-09-01 00:00:00
abstract：:Intestinal CD8αα intraepithelial T lymphocytes (T-IELs) have a key role in mucosal immunity and, unlike other T cells, were proposed to differentiate locally. In apparent contradiction, these cells were also shown to originate from a wave of thymus migrants colonizing the gut in the first 3 weeks after birth. We here ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2010.47
更新日期：2011-01-01 00:00:00
abstract：:Cholera is a severe diarrheal disease caused by the bacterium Vibrio cholerae (V. cholerae) that results in 3-4 million cases globally with 100,000-150,000 deaths reported annually. Mostly confined to developing nations, current strategies to control the spread of cholera include the provision of safe drinking water a...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0159-z
更新日期：2019-07-01 00:00:00
abstract：:Secondary bacterial pneumonia is a significant complication of severe influenza infection and Staphylococcus aureus and Streptococcus pneumoniae are the primary pathogens of interest. IL-22 promotes S. aureus and S. pneumoniae host defense in the lung through epithelial integrity and induction of antimicrobial peptide...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0188-7
更新日期：2019-09-01 00:00:00
abstract：:Development of effective tuberculosis vaccines is hampered by insufficient understanding of protective immunity. Here, Woodworth et al.1 show secondary effector CD4 T cells generated after Mtb challenge of H56/CAF01 vaccinated mice display superior lung homing compared with primary effectors. Vaccination generates lar...
journal_title：Mucosal immunology
pub_type： 评论,杂志文章
doi：10.1038/mi.2016.110
更新日期：2017-03-01 00:00:00
abstract：:Although an enrichment of orally derived bacteria is reported in the gut microbiota of patients with several diseases, it is mostly unknown whether oral bacteria can colonize and induce intestinal inflammation. In a recent paper in Science, Atarashi et al.1 from Kenya Honda's laboratory show that a subset of orally de...
journal_title：Mucosal immunology
pub_type： 评论,杂志文章
doi：10.1038/mi.2017.116
更新日期：2018-03-01 00:00:00
abstract：:Children born by cesarean section (CS) have an increased risk of developing inflammatory bowel disease (IBD), possibly due to skewed microbial colonization during birth and consequently impaired bacterial stimulation of the developing immune system. The aim of this study was to investigate the association between CS a...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0207-8
更新日期：2019-11-01 00:00:00
abstract：:Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of the current pneumonia cases...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2016.41
更新日期：2017-01-01 00:00:00
abstract：:Women with asymptomatic Neisseria gonorrhoeae infection are at risk of developing pelvic inflammatory disease (PID) if the bacteria ascend from the endocervix into the uterus and oviducts. Factors that affect disease severity, ranging from mild discomfort to severe inflammation, pain, and infertility, remain elusive. ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2015.122
更新日期：2016-07-01 00:00:00
abstract：:T helper type (Th17) cytokines such as interleukin (IL)-17A and IL-22 are important in maintaining mucosal barrier function and may be important in the pathogenesis of inflammatory bowel diseases (IBDs). Here, we analyzed cells from the colon of IBD patients and show that Crohn's disease (CD) patients had significantl...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2013.31
更新日期：2014-01-01 00:00:00
abstract：:Viral respiratory tract infections (RTI) pose a high burden on the youngest members of our society. Several risk factors are known for severe viral respiratory disease. However, a large proportion of the severe RTI cannot be explained by these risk factors. A growing body of evidence shows that the composition of the ...
journal_title：Mucosal immunology
pub_type： 杂志文章,评审
doi：10.1038/mi.2013.93
更新日期：2014-03-01 00:00:00
abstract：:Celiac disease (CD) is a chronic small intestinal inflammation precipitated by gluten ingestion. According to case reports, interferon (IFN)-α administration may induce development of overt CD. Plasmacytoid dendritic cells (PDCs) were thought to be the source of IFN-α and promote a T helper type 1 response leading to ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2012.136
更新日期：2013-09-01 00:00:00
abstract：:Group 3 innate lymphoid cells (ILC3s), a subset of the innate lymphoid cells, are abundantly present in the intestine and are crucial regulators of intestinal inflammation. Brg1 (Brahma-related gene 1), a catalytic subunit of the mammalian SWI-SNF-like chromatin-remodeling BAF complex, regulates the development and fu...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-020-0317-3
更新日期：2021-01-01 00:00:00
abstract：:Cross-presentation of cellular antigens is crucial for priming CD8(+) T cells, and generating immunity to intracellular pathogens--particularly viruses. It is unclear which intestinal phagocytes perform this function in vivo. To address this, we examined dendritic cells (DCs) from the intestinal lymph of IFABP-tOVA 23...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2014.40
更新日期：2015-01-01 00:00:00
abstract：:The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2016.35
更新日期：2017-01-01 00:00:00
abstract：:Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections, especially in infants. Lung neutrophilia is a hallmark of RSV disease but the mechanism by which neutrophils are recruited and activated is unclear. Here, we investigate the innate immune signaling pathways underlying ne...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0190-0
更新日期：2019-09-01 00:00:00
abstract：:The extent to which tissue-specific viral infections generate memory T cells specifically adapted to and maintained within the target infection site is unknown. Here, we show that respiratory virus-specific memory T cells in mice and humans are generated and maintained in compartmentalized niches in lungs, distinct fr...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2013.67
更新日期：2014-05-01 00:00:00
abstract：:Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2014.57
更新日期：2015-03-01 00:00:00
abstract：:Mucus, with its burden of inspired particulates and pathogens, is cleared from mucosal surfaces of the airways by cilia beating within the periciliary layer (PCL). The PCL is held to be "watery" and free of mucus by thixotropic-like forces arising from beating cilia. With radii of gyration ~250 nm, however, polymeric ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2012.81
更新日期：2013-03-01 00:00:00
abstract：:The roles of macrophages in type 2-driven inflammation and fibrosis remain unclear. Here, using CD11b-diphtheria toxin receptor (DTR) transgenic mice and three models of interleukin 13 (IL-13)-dependent inflammation, fibrosis, and immunity, we show that CD11b(+) F4/80(+) Ly6C(+) macrophages are required for the mainte...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2015.34
更新日期：2016-01-01 00:00:00
