2021
DOI: 10.1172/jci.insight.141326
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STAT4 is expressed in neutrophils and promotes antimicrobial immunity

Abstract: Signal transducer and activator of transcription 4 (STAT4) is expressed in hematopoietic cells and plays a key role in the differentiation of T helper 1 cells. Although STAT4 is required for immunity to intracellular pathogens, the T cell-independent protective mechanisms of STAT4 are not clearly defined. In this report, we demonstrate that STAT4-deficient mice are acutely sensitive to methicillin-resistant Staphylococcus aureus (MRSA) infection. We show that STAT4 is expressed in neutrophils and activated by … Show more

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Cited by 29 publications
(15 citation statements)
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“…Neutrophil recruitment and activation are also capable of inflicting tissue damage and prolonged inflammation. Neutrophil-driven inflammation is a common mechanism underlying many pathological conditions, including cardiovascular, acute respiratory, neurodegenerative, metabolic and autoimmune diseases, sepsis, and asthma ( 2 , 6 , 7 , 11 , 17 , 18 , 41 ).…”
Section: Discussionmentioning
confidence: 99%
“…Neutrophil recruitment and activation are also capable of inflicting tissue damage and prolonged inflammation. Neutrophil-driven inflammation is a common mechanism underlying many pathological conditions, including cardiovascular, acute respiratory, neurodegenerative, metabolic and autoimmune diseases, sepsis, and asthma ( 2 , 6 , 7 , 11 , 17 , 18 , 41 ).…”
Section: Discussionmentioning
confidence: 99%
“…Animals were kept on a 12-hour light/dark cycle with ad libitum access to food and water under pathogen-free conditions. Stat4 fl/fl were generated previously 8 and crossed with Ldlr -/mice (JAX, Cat:#002207) and either with B6.129P2-Lyz2tm1(cre)Ifo/J or B6.Cg-Tg(S100A8-cre,-EGFP)1Ilw/J transgenic mice (JAX, Cat:#004781; Cat:#021614, respectively) to generate control Stat4 fl/fl Ldlr -/-, myeloid-specific Stat4 ΔLysM Ldlr -/and neutrophil-specific Stat4 ΔS100A8 Ldlr -/-Stat4-deficient Ldlr -/mice. To induce chronic hypercholesterolemia and advanced atherosclerosis, 8-12-week-old male mice were placed on a high fat diet with 0.15% added cholesterol (HFD-C, fat: 60% kcal; carbohydrate: 26% kcal, Bio-Serv F3282) for 28 weeks until sacrifice.…”
Section: Animals and Study Designmentioning
confidence: 99%
“…7 More recently, we have demonstrated that STAT4 is expressed and readily activated in neutrophils and is required for host defense against methicillin-resistant Staphylococcus aureus via several STAT4-dependent neutrophil defense mechanisms including chemotaxis, ROS production, and NET formation. 8 We therefore hypothesized that STAT4 in neutrophils would participate in atherosclerosis development and plaque instability. Here, we demonstrate that neutrophil-specific STAT4 deficiency improves atherosclerotic burden and plaque stability via reductions in neutrophilia, basal neutrophil activation, and in vivo migration to atherosclerotic plaques.…”
Section: Introductionmentioning
confidence: 99%
“…CCL5 ( RANTES ), CCR5, CD4 , STAT4 , IL10 , and LYZ were significantly upregulated in LDNs, whereas CXCL8 ( IL8 ), STAT1 , IFNAR1 , NFKB1 , TICAM1 , and TNF were significantly downregulated ( Figure 2 ) ( La Manna et al., 2019 ). CCL5 , STAT4 , CD4 , LYZ upregulation in neutrophils have been associated with inflammation and neutrophil antimicrobial activity ( Flanagan and Lionetti, 1955 ; Pan et al., 2000 ; Hartl et al., 2008 ; Keeter et al., 2020 ; Mehrpouya-Bahrami et al., 2021 ). IL-10 and IFNAR1 signaling have been associated with susceptibility to TB and poor outcomes of disease ( Verbon et al., 1999 ; Bonecini-Almeida et al., 2004 ; Jamil et al., 2007 ; Dorhoi et al., 2014 ; Huynh et al., 2018 ; Zhang et al., 2018 ; Moreira-Teixeira et al., 2020 ).…”
Section: Activity Of Ldns Isolated From Tb Patientsmentioning
confidence: 99%