Abstract:
BACKGROUND:Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host's signature of the inflammatory/oxidative state and provide information regarding the progression of clinical disease. METHODS:MPs were harvested from supernatants of human peripheral blood mononuclear cells in vitro incubated with Tc (control: LPS treated), plasma of seropositive humans with a clinically asymptomatic (CA) or symptomatic (CS) disease state (vs. normal/healthy [NH] controls), and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of mφ activation by flow cytometry, cytokine profile by means of an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by means of colorimetric and fluorometric assays. RESULTS:Tc- and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile, and nitric oxide (∙NO) release in human THP-1 mφs. LPS-MPs were more immunostimulatory than Tc-MPs. Endothelial cells, T lymphocytes, and mφs were the major source of MPs shed in the plasma of chagasic humans and experimentally infected mice. The CS and CA (vs. NH) MPs elicited >2-fold increase in NO and mitochondrial oxidative stress in THP-1 mφs; however, CS (vs. CA) MPs elicited a more pronounced and disease-state-specific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2, and CCL3), cytokine release (IL-2 + IFN-γ > GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of nonvaccinated/infected mice induced 7.5-fold and 40% increases in ∙NO and IFN-γ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. CONCLUSION:Circulating MPs reflect in vivo levels of an oxidative, nitrosative, and inflammatory state, and have potential utility in evaluating disease severity and the efficacy of vaccines and drug therapies against CCM.
journal_name
J Innate Immunjournal_title
Journal of innate immunityauthors
Chowdhury IH,Koo SJ,Gupta S,Liang LY,Bahar B,Silla L,Nuñez-Burgos J,Barrientos N,Zago MP,Garg NJdoi
10.1159/000451055subject
Has Abstractpub_date
2017-01-01 00:00:00pages
203-216issue
2eissn
1662-811Xissn
1662-8128pii
000451055journal_volume
9pub_type
杂志文章abstract::Glucocorticoid-induced leucine zipper (GILZ) is a potent anti-inflammatory protein, the expression of which is mainly induced by glucocorticoids (GCs) in haematopoietic cells. GILZ regulates signal transduction pathways of inflammation and plays a role in cell survival. The objective of this study was to evaluate the ...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000439052
更新日期:2016-01-01 00:00:00
abstract::In in vitro experiments, Chlamydia pneumoniae has been shown to infect macrophages and to accelerate foam cell formation. It has been hypothesized that the C. pneumoniae infection affects foam cell formation by suppressing the expression of liver X receptors (LXR), but whether such an event occurs in human atheroscler...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000327522
更新日期:2011-01-01 00:00:00
abstract::Neutrophils are the most abundant cell type involved in the innate immune response. They are rapidly recruited to sites of injury or infection where they engulf and kill invading microorganisms. Neutrophil apoptosis, the process of programmed cell death that prevents the release of neutrophil histotoxic contents, is t...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000284367
更新日期:2010-01-01 00:00:00
abstract::Porphyromonas gingivalis produces proteases capable of degrading cytokines, host heme proteins and some antimicrobial peptides. In this study, we show that P. gingivalis culture supernatants fully or partially degrade human neutrophil peptide alpha-defensins and human beta-defensins after 30 min. This observation sugg...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000181015
更新日期:2009-01-01 00:00:00
abstract::Klebsiella pneumoniae is a common cause of hospital-acquired pneumonia. Granzymes (gzms), mainly found in cytotoxic lymphocytes, have been implicated as mediators of infection and inflammation. We here sought to investigate the role of gzmA and gzmB in the host response to K. pneumoniae-induced airway infection and se...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000443401
更新日期:2016-01-01 00:00:00
abstract::Historically, the prevailing view in the field of invertebrate immunity was that invertebrates that do not possess acquired adaptive immunity rely on innate mechanisms with low specificity and no memory. Several recent studies have shaken this paradigm and suggested that the immune defenses of invertebrates are more c...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000345909
更新日期:2013-01-01 00:00:00
abstract::The role of the transcription factor nuclear factor of activated T cells (NFAT) was initially identified in T and B cell gene expression, but its role in regulating gene expression in macrophages during sepsis is not known. Our data show that NFATc3 regulates expression of inducible nitric oxide synthase (iNOS) in mac...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000362647
更新日期:2014-01-01 00:00:00
abstract::The phagocyte NADPH oxidase, crucial for innate immunity, is dormant in resting cells, but becomes activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. In activation of the oxidase, the multidomain protein p67(phox)plays a central role: it translocates to the membrane as a ternary...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000235656
更新日期:2009-01-01 00:00:00
abstract::Mucosal surfaces line our body cavities and provide the interaction surface between commensal and pathogenic microbiota and the host. The barrier function of the mucosal layer is largely maintained by gel-forming mucin proteins that are secreted by goblet cells. In addition, mucosal epithelial cells express cell-bound...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000453594
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Alpha-synuclein (αS) is a nerve cell protein associated with Parkinson disease (PD). Accumulation of αS within the enteric nervous system (ENS) and its traffic from the gut to the brain are implicated in the pathogenesis and progression of PD. αS has no known function in humans and the reason for its accumul...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000477990
更新日期:2017-01-01 00:00:00
abstract::Toll-like receptors (TLRs) are key molecules in innate immunity that recognize a variety of pathogen-associated molecular patterns. Activation of TLRs by their agonists initiates several signaling cascades, which eventually result in the expression of immune modifiers. Despite the fact that MCPIP1 is reported as an im...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000339826
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Pseudomonas aeruginosa (PS) infection results in severe morbidity and mortality, especially in immune-deficient populations. Aerobic exercise (AE) modulates the immune system, but its effects on the outcomes of pulmonary PS infection in elderly mice are unknown. METHODS:BALB/c mice (24 weeks old) were rando...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000488953
更新日期:2018-01-01 00:00:00
abstract::Psoriasis is one of the most common immune-mediated disorders. There is evidence that it is mediated by Th1 and, more recently, Th17 cells. The cytokine pattern, particularly the dominance of TNF-α, implicates the innate immune system in psoriasis pathogenesis. Of the many components of the innate immune system known ...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000328011
更新日期:2011-01-01 00:00:00
abstract::To protect against viral infection, the immune response is critically dependent on innate sensing mechanisms to provide rapid detection of pathogens and allow for the development of an appropriate adaptive immune response. Mounting evidence suggests that mechanistic differences in the sensing of viruses by the innate ...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000226247
更新日期:2009-01-01 00:00:00
abstract::L-ficolin, one of the complement lectins found in human serum, is a novel pattern recognition molecule that can specifically bind to microbial carbohydrates, thereby activating the lectin complement pathway and mounting a protective innate immune response. However, little is known about the role of L-ficolin during vi...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000335670
更新日期:2012-01-01 00:00:00
abstract::NK cells play a central role in innate immunity, acting directly through cell-mediated cytotoxicity and by secreting cytokines. TNFα activation of TNFR2 enhances NK cell cytotoxicity, but its effects on the other essential function of NK cells - cytokine production, for which IFNγ is paramount - are poorly defined. We...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000448077
更新日期:2016-01-01 00:00:00
abstract::The concept that macrophages play an active role in inflammatory responses began its development in the late 1800s with the now iconic studies by Elie Metchnikoff using starfish larvae and Daphnia [reviewed in Kaufmann SHE: Nat Immunol 2008;9:705-712 and Cavaillon JM: J Leukoc Biol 2011;90:413-424]. Based on his obser...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000336025
更新日期:2012-01-01 00:00:00
abstract::Mannose-binding lectin (MBL) is an innate immune system pattern recognition protein that kills a wide range of pathogenic microbes through complement activation. A substantial proportion of all human populations studied to date have MBL deficiency due to MBL2 polymorphisms, which potentially increases susceptibility t...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000228159
更新日期:2010-01-01 00:00:00
abstract::Streptococcus pyogenes is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although S. pyogenes are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emph...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000317635
更新日期:2010-01-01 00:00:00
abstract::We demonstrated recently that Francisella tularensis profoundly impairs human neutrophil apoptosis, but how this is achieved is largely unknown. Herein we used human oligonucleotide microarrays to test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, and now demonstrate that F. t...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000342430
更新日期:2013-01-01 00:00:00
abstract::The host innate immune response, including the production of type-I IFN, represents the primary line of defense against invading viral pathogens. Of the hundreds of IFN-stimulated genes (ISGs) discovered to date, ISG15 was one of the first identified and shown to encode a ubiquitin-like protein that functions, in part...
journal_title:Journal of innate immunity
pub_type: 杂志文章,评审
doi:10.1159/000226245
更新日期:2009-01-01 00:00:00
abstract::Despite the extensive efforts that have been made to combat acquired immune deficiency syndrome (AIDS), the number of people infected each year with human immunodeficiency virus type 1 (HIV-1) is still increasing worldwide, and a safe and effective vaccine to control HIV infection is urgently needed. Recently, the nat...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000329226
更新日期:2012-01-01 00:00:00
abstract::As a key molecule in the antiviral innate immune response, the activation of TANK-binding kinase 1 (TBK1) is under tight regulation. In this report, we identified phosphatidylserine-specific phospholipase PLA1A as a host factor that modulates the TBK1 activation. Knockdown of PLA1A expression suppressed the innate imm...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000489832
更新日期:2018-01-01 00:00:00
abstract::Hemolytic uremic syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure, is caused by enterohemorrhagic Shiga toxin (Stx)-producing bacteria, which mainly affect children. Besides Stx, the inflammatory response mediated by neutrophils (PMN) is essential to HUS e...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000445770
更新日期:2016-01-01 00:00:00
abstract::Early interactions between natural killer (NK) and dendritic cells (DC) shape the immune response at the frontier of innate and adaptive immunity. Activated NK cells participate in maturation or deletion of DCs that remain immature. We previously demonstrated that infection with a high virulence (HV) population of the...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000350242
更新日期:2013-01-01 00:00:00
abstract::Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate γ-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cel...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000350234
更新日期:2013-01-01 00:00:00
abstract::Different liver cell types are endowed with immunological properties, including cell-intrinsic innate immune functions that are important to initially control pathogen infections. However, a full landscape of expression and functionality of the innate immune signaling pathways in the major human liver cells is still m...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000489966
更新日期:2018-01-01 00:00:00
abstract::The complement-like protein thioester-containing protein 1 (TEP1) is the hallmark effector molecule against Plasmodium ookinetes in the malaria vector Anopheles gambiae. We have previously shown that the knockdown of the noncatalytic clip domain serine protease CLIPA2 increased TEP1-mediated killing rendering mosquito...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000443883
更新日期:2016-01-01 00:00:00
abstract::We characterized the dual oxidase (Duox) gene in the major Indian malaria vector Anopheles stephensi, which regulates the generation of reactive oxygen species. The AsDuox gene encodes for a 1,475-amino-acid transmembrane protein that contains an N-terminal noncytoplasmic heme peroxidase domain, a calcium-binding doma...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000497417
更新日期:2019-01-01 00:00:00
abstract::Withdrawal of iron from serum (hypoferraemia) is a conserved innate immune antimicrobial strategy that can withhold this critical nutrient from invading pathogens, impairing their growth. Hepcidin (Hamp1) is the master regulator of iron and its expression is induced by inflammation. Mice lacking Hamp1 from birth rapid...
journal_title:Journal of innate immunity
pub_type: 杂志文章
doi:10.1159/000447713
更新日期:2016-01-01 00:00:00