https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22098 Wed 19 Apr 2023 16:41:23 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48016 To the Editor: The major 17q12-21 asthma susceptibility and exacerbation locus1 has been identified as the only genetic locus that is also reproducibly associated with total white blood cell count.2 However, it is not known whether there is a common gene within this locus that links these phenotypic traits. The colony-stimulating factor-3 (CSF3) gene, alternatively known as G-CSF, resides within this locus. CSF3 binds exclusively to CSF3 receptor (CSF3R, or CD114/G-CSFR), which is highly expressed on mature neutrophils and to a lesser extent on mononuclear cells, platelets, and lung interstitial stromal cells. Although CSF3R/CD114 signaling can dictate the intensity of the host defense inflammatory response during bacterial infection by regulating neutrophil granulopoiesis and trafficking, its role in the infection-dependent transition to persistent, severe asthma has not been investigated. Neonatal colonization of the nasopharynx by potentially pathogenic bacteria including Streptococcus pneumoniae is also a risk factor for asthma development.3 The Childhood Asthma Study found that children with atopy and chronic wheeze at age 5 years were twice as likely to have been colonized with S pneumoniae as neonates.4 The authors suggest that transient incursions of nasopharyngeal bacteria into the lower airways triggered by a fever-causing viral respiratory infection (respiratory syncytial virus or influenza virus) increases the risk of developing persistent asthma in atopic children. However, a plausible mechanism linking these cofactors is yet to be identified. In this study, we tested the hypothesis that CSF3-CSF3R signaling dictates the severity of infectiondependent asthma at a cellular and molecular level.]]> Wed 15 Feb 2023 10:19:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50107 Wed 12 Jul 2023 13:43:56 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36818 Wed 08 Jul 2020 11:42:42 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44806 Wed 01 May 2024 12:05:04 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54370 Tue 20 Feb 2024 19:58:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:41995 Tue 16 Aug 2022 16:37:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51598 Tue 12 Sep 2023 12:25:08 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33773 Thu 27 Jan 2022 15:56:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48574 Thu 24 Aug 2023 15:19:53 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16919 Sat 24 Mar 2018 08:00:28 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22164 Sat 24 Mar 2018 07:14:59 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54966 Mon 25 Mar 2024 12:11:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40097 Fri 22 Jul 2022 13:41:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:46346 via NF-κB, eicosanoid biosynthesis via the lipoxygenase pathway and IL-2 biosynthesis (all P<.01). Sputum macrophage number and the ES for most macrophage signatures were higher in the TAC3 group compared to TAC1 and TAC2 asthmatics. However, a high enrichment was found in TAC1 for 3 modules showing inflammatory pathways linked to Toll-like and TNF receptor activation and arachidonic acid metabolism (P<.001) and in TAC2 for the inflammasome and interferon signalling pathways (P<.001). Data were validated in the ADEPT cohort. Module analysis provides additional information compared to conventional M1 and M2 classification. TR-Mφ were enriched in TAC3 and associated with mitochondrial function. Conclusions: Macrophage activation is attenuated in severe granulocytic asthma highlighting defective innate immunity except for specific subsets characterized by distinct inflammatory pathways.]]> Fri 18 Nov 2022 10:08:37 AEDT ]]>