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Mucosal Immunology

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https://www.readbyqxmd.com/read/28612844/nlrp3-inflammasome-pathway-has-a-critical-role-in-the-host-immunity-against-clinically-relevant-acinetobacter-baumannii-pulmonary-infection
#1
N Dikshit, S D Kale, H J Khameneh, V Balamuralidhar, C Y Tang, P Kumar, T P Lim, T T Tan, A L Kwa, A Mortellaro, B Sukumaran
The opportunistic Gram-negative bacterium Acinetobacter baumannii (AB) is a leading cause of life-threatening nosocomial pneumonia. Outbreaks of multidrug resistant (MDR)-AB belonging to international clones (ICs) I and II with limited treatment options are major global health threats. However, the pathogenesis mechanisms of various AB clonal groups are understudied. Although inflammation-associated interleukin-1β (IL-1β) levels and IL-1 receptor antagonist polymorphisms were previously implicated in MDR-AB-related pneumonia in patients, whether inflammasomes has any role in the host defense and/or pathogenesis of clinically relevant A...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28612843/tricellulin-is-regulated-via-interleukin-13-receptor-%C3%AE-2-affects-macromolecule-uptake-and-is-decreased-in-ulcerative-colitis
#2
S M Krug, C Bojarski, A Fromm, I M Lee, P Dames, J F Richter, J R Turner, M Fromm, J-D Schulzke
In the two inflammatory bowel diseases, ulcerative colitis (UC) and Crohn's disease (CD), altered expression of tight junction (TJ) proteins leads to an impaired epithelial barrier including increased uptake of luminal antigens supporting the inflammation. Here, we focused on regulation of tricellulin (Tric), a protein of the tricellular TJ essential for the barrier against macromolecules, and hypothesized a role in paracellular antigen uptake. We report that Tric is downregulated in UC, but not in CD, and that its reduction increases the passage of macromolecules...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28612842/gastrointestinal-inflammation-by-gut-microbiota-disturbance-induces-memory-impairment-in-mice
#3
S-E Jang, S-M Lim, J-J Jeong, H-M Jang, H-J Lee, M J Han, D-H Kim
In this study, we tested our hypothesis regarding mechanistic cross-talk between gastrointestinal inflammation and memory loss in a mouse model. Intrarectal injection of the colitis inducer 2,4,6-trinitrobenzenesulfonic acid (TNBS) in mice caused colitis via activation of nuclear factor (NF)-κB and increase in membrane permeability. TNBS treatment increased fecal and blood levels of lipopolysaccharide (LPS) and the number of Enterobacteriaceae, particularly Escherichia coli (EC), in the gut microbiota composition, but significantly reduced the number of Lactobacillus johnsonii (LJ)...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28612841/il-17-driven-intestinal-fibrosis-is-inhibited-by-itch-mediated-ubiquitination-of-hic-5
#4
J Paul, A K Singh, M Kathania, T L Elviche, M Zeng, V Basrur, A L Theiss, K Venuprasad
Intestinal fibrosis is a major complication in inflammatory bowel diseases, but the regulatory mechanism that inhibits fibrosis remains unclear. Here we demonstrate that Itch(-/-)myofibroblasts express increased amounts of profibrotic collagen type I and α-SMA in response to IL-17. Mechanistically, we demonstrate that Itch directly binds to HIC-5 and targets it for K63-linked ubiquitination to inhibit IL-17-driven intestinal fibrosis. Reconstitution of Itch(-/-) myofibroblasts with wild-type Itch but not the Itch-C830A mutant normalized the expression of profibrotic genes...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28612840/toll-like-receptor-3-in-nasal-cd103-dendritic-cells-is-involved-in-immunoglobulin-a-production
#5
H Takaki, S Kure, H Oshiumi, Y Sakoda, T Suzuki, A Ainai, H Hasegawa, M Matsumoto, T Seya
Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI:C was endocytosed into CD103(+) dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-γ production...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28612839/citrobacter-rodentium-a-model-enteropathogen-for-understanding-the-interplay-of-innate-and-adaptive-components-of-type-3-immunity
#6
REVIEW
D J Silberger, C L Zindl, C T Weaver
Citrobacter rodentium is a natural murine intestinal pathogen that shares a core set of virulence factors with the related human pathogens enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). C. rodentium is now the most widely used small animal model for studying the molecular underpinnings of EPEC and EHEC infections in vivo, including: enterocyte attachment; virulence; colonization resistance; and mucosal immunity. In this review, we discuss type 3 immunity in the context of C. rodentium infection and discuss recent publications that use this model to understand how the innate and adaptive components of immunity intersect to mediate host protection against enteric pathogens and maintain homeostasis with the microbiota...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28589946/elevated-prostaglandin-e2-post-bone-marrow-transplant-mediates-interleukin-1%C3%AE-related-lung-injury
#7
G J Martínez-Colón, Q M Taylor, C A Wilke, A B Podsiad, B B Moore
Hematopoietic stem cell transplant (HSCT) treats or cures a variety of hematological and inherited disorders. Unfortunately, patients who undergo HSCT are susceptible to infections by a wide array of opportunistic pathogens. Pseudomonas aeruginosa bacteria can have life-threatening effects in HSCT patients by causing lung pathology that has been linked to high levels of the potent pro-inflammatory cytokine, interleukin-1β (IL-1β). Using a murine bone marrow transplant (BMT) model, we show that overexpression of prostaglandin E2 (PGE2) post-BMT signals via EP2 or EP4 to induce cyclic adenosine monophosphate (cAMP), which activates protein kinase A or the exchange protein activated by cAMP (Epac) to induce cAMP response element binding-dependent transcription of IL-1β leading to exacerbated lung injury in BMT mice...
June 7, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28537249/airway-t-cells-protect-against-rsv-infection-in-the-absence-of-antibody
#8
E Kinnear, L Lambert, J U McDonald, H M Cheeseman, L J Caproni, J S Tregoning
Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8(+) Trm cells (CD103(+)/CD69(+)) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice...
May 24, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513596/an-innate-defense-peptide-bpifa1-splunc1-restricts-influenza-a-virus-infection
#9
K M Akram, N A Moyo, G H Leeming, L Bingle, S Jasim, S Hussain, A Schorlemmer, A Kipar, P Digard, R A Tripp, R V Shohet, C D Bingle, J P Stewart
The airway epithelium secretes proteins that function in innate defense against infection. Bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism, we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513595/hiv-2-infection-is-associated-with-preserved-galt-homeostasis-and-epithelial-integrity-despite-ongoing-mucosal-viral-replication
#10
S M Fernandes, A R Pires, P Matoso, C Ferreira, H Nunes-Cabaço, L Correia, E Valadas, J Poças, P Pacheco, H Veiga-Fernandes, R B Foxall, A E Sousa
The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513594/regionally-compartmentalized-resident-memory-t-cells-mediate-naturally-acquired-protection-against-pneumococcal-pneumonia
#11
N Ms Smith, G A Wasserman, F T Coleman, K L Hilliard, K Yamamoto, E Lipsitz, R Malley, H Dooms, M R Jones, L J Quinton, J P Mizgerd
As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513593/jak3-deficiency-blocks-innate-lymphoid-cell-development
#12
M L Robinette, M Cella, J B Telliez, T K Ulland, A D Barrow, K Capuder, S Gilfillan, L-L Lin, L D Notarangelo, M Colonna
Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID). Defects in this form of SCID are restricted to the immune system, which led to the development of immunosuppressive JAK inhibitors. We find that the B6.Cg-Nr1d1(tm1Ven)/LazJ mouse line purchased from Jackson Laboratories harbors a spontaneous mutation in Jak3, generating a SCID phenotype and an inability to generate antigen-independent professional cytokine-producing innate lymphoid cells (ILCs)...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513592/ifn-%C3%AE-increases-susceptibility-to-influenza-a-infection-through-suppression-of-group-ii-innate-lymphoid-cells
#13
D Califano, Y Furuya, S Roberts, D Avram, A N J McKenzie, D W Metzger
Increased levels of interferon-γ (IFN-γ) are routinely observed in the respiratory tract following influenza virus infection, yet its potential role remains unclear. We now demonstrate that influenza-induced IFN-γ restricts protective innate lymphoid cell group II (ILC2) function in the lung following challenge with the pandemic H1N1 A/CA/04/2009 (CA04) influenza virus. Specifically, IFN-γ deficiency resulted in enhanced ILC2 activity, characterized by increased production of interleukin (IL)-5 and amphiregulin, and improved tissue integrity, yet no change in ILC2 numbers, viral load or clearance...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28488693/icos-protects-against-mortality-from-acute-lung-injury-through-activation-of-il-5-ilc2s
#14
C L Hrusch, S T Manns, D Bryazka, J Casaos, C A Bonham, M R Jaffery, K M Blaine, K A M Mills, P A Verhoef, A O Adegunsoye, J W Williams, M Y Tjota, T V Moore, M E Strek, I Noth, A I Sperling
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis...
May 10, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#15
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28422188/resolvin-d1-enhances-the-resolution-of-lung-inflammation-caused-by-long-term-pseudomonas-aeruginosa-infection
#16
M Codagnone, E Cianci, A Lamolinara, V C Mari, A Nespoli, E Isopi, D Mattoscio, M Arita, A Bragonzi, M Iezzi, M Romano, A Recchiuti
Pseudomonas aeruginosa lung infection is a main cause of disability and mortality worldwide. Acute inflammation and its timely resolution are crucial for ensuring bacterial clearance and limiting tissue damage. Here, we investigated protective actions of resolvin (Rv) D1 in lung infection induced by the RP73 clinical strain of P. aeruginosa. RvD1 significantly diminished bacterial growth and neutrophil infiltration during acute pneumonia caused by RP73. Inoculum of RP73, immobilized in agar beads, resulted in persistent lung infection up to 21 days, leading to a non resolving inflammation reminiscent of human pathology...
April 19, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28422187/a-sphingosine-1-phosphate-receptor-1-agonist-inhibits-tertiary-lymphoid-tissue-reactivation-and-hypersensitivity-in-the-lung
#17
C A Huppé, P Blais Lecours, A Lechasseur, D R Gendron, A M Lemay, E Y Bissonnette, M R Blanchet, C Duchaine, M C Morissette, H Rosen, D Marsolais
Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P1) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P1 caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis...
April 19, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28422186/high-fat-diet-induces-systemic-b-cell-repertoire-changes-associated-with-insulin-resistance
#18
T D Pham, M H Y Chng, K M Roskin, K J L Jackson, K D Nguyen, J Glanville, J-Y Lee, E G Engleman, S D Boyd
The development of obesity-associated insulin resistance is associated with B-lymphocyte accumulation in visceral adipose tissue (VAT) and is prevented by B-cell ablation. To characterize potentially pathogenic B-cell repertoires in this disorder, we performed high-throughput immunoglobulin (Ig) sequencing from multiple tissues of mice fed high-fat diet (HFD) and regular diet (RD). HFD significantly changed the biochemical properties of Ig heavy-chain complementarity-determining region-3 (CDRH3) sequences, selecting for IgA antibodies with shorter and more hydrophobic CDRH3 in multiple tissues...
April 19, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401939/mdr1-deficiency-impairs-mitochondrial-homeostasis-and-promotes-intestinal-inflammation
#19
G-T Ho, R E Aird, B Liu, R K Boyapati, N A Kennedy, D A Dorward, C L Noble, T Shimizu, R N Carter, E T S Chew, N M Morton, A G Rossi, R B Sartor, J P Iredale, J Satsangi
The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux transporter that is highly expressed in the colon. In mice, loss of MDR1 function results in colitis with similarities to human inflammatory bowel diseases (IBD). Here, we show that MDR1 has an unexpected protective role for the mitochondria where MDR1 deficiency results in mitochondrial dysfunction with increased mitochondrial reactive oxygen species (mROS) driving the development of colitis. Exogenous induction of mROS accelerates, while inhibition attenuates colitis in vivo; these effects are amplified in MDR1 deficiency...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401938/novel-protective-mechanism-for-interleukin-33-at-the-mucosal-barrier-during-influenza-associated-bacterial-superinfection
#20
K M Robinson, K Ramanan, M E Clay, K J McHugh, H E Rich, J F Alcorn
Influenza A is a highly contagious respiratory virus that causes seasonal epidemics and occasional worldwide pandemics. The primary cause of influenza-related mortality is bacterial superinfection. There are numerous mechanisms by which preceding influenza infection attenuates host defense, allowing for increased susceptibility to bacterial pneumonia. Herein, we demonstrate that influenza inhibits Staphylococcus aureus-induced production of interleukin-33 (IL-33). Restoration of IL-33 during influenza A and methicillin-resistant S...
April 12, 2017: Mucosal Immunology
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