Co-stimulation with LPS or Poly I:C markedly enhances the anti-platelet immune response and severity of fetal and neonatal alloimmune thrombocytopenia

2013 ◽  
Vol 110 (12) ◽  
pp. 1250-1258 ◽  
Author(s):  
Conglei Li ◽  
Pingguo Chen ◽  
Brian Vadasz ◽  
Li Ma ◽  
Hui Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infections ◽  
Poly I:C ◽  
Polyinosinic:Polycytidylic Acid ◽  
Immune Mediated ◽  
Life Threatening ◽  
Β3 Integrin ◽  
Severe Pathology ◽  
Alloimmune Thrombocytopenia ◽  
First Time

SummaryFetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal antibodies against fetal/neonatal platelets. FNAIT is also linked with miscarriages, although the incidence and mechanisms of fetal death have not been well studied. Integrin αIIbβ3 (GPIIbIIIa) and the GPIbα complex are major glycoproteins expressed on platelets and are also major antigens targeted in autoimmune thrombocytopenia (ITP), but reported cases of anti-GPIb-mediated FNAIT are rare. Bacterial and viral infections have been causally linked with the pathogenesis of immune-mediated thrombocytopenia (ITP); however, it is unknown whether these infections contribute to the severity of FNAIT. Here, immune responses against platelet antigens were examined by transfusing wild-type (WT) mouse platelets into β3-/- or GPIbα-/- mice. To mimic bacterial or viral infections, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C) were injected intraperitoneally following platelet transfusions. The FNAIT model was established by breeding the immunised female mice with WT male mice. We demonstrated for the first time that the platelet GPIbα has lower immunogenicity compared to β3 integrin. Interestingly, co-stimulation with LPS or Poly I:C markedly enhanced the immune response against platelet GPIbα and caused severe pathology of FNAIT (i.e. miscarriages). LPS or Poly I:C also enhanced the immune response against platelet β3 integrin. Our data suggest that bacterial and viral infections facilitate the anti-platelet GPIbα response, which may lead to a severe non-classical FNAIT (i.e. miscarriage but not neonatal bleeding) that has not been adequately reported in humans.

Murine Model of Fetal and Neonatal Alloimmune Thrombocytopenia Mediated by Anti-GPIb α Versus Anti-β3 Integrin Antibodies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 704-704
Author(s):  
Siavash Piran ◽  
Pingguo Chen ◽  
Guangheng Zhu ◽  
Hong Yang ◽  
Michelle Webster ◽  
...  
Keyword(s):  
Maternal Antibody ◽  
Igg Antibody ◽  
Group I ◽  
Life Threatening ◽  
Antibody Titers ◽  
Β3 Integrin ◽  
Group Ii ◽  
Severe Pathology ◽  
Alloimmune Thrombocytopenia ◽  
Platelet Transfusions

Abstract Fetal and neonatal alloimmune thrombocytopenia (FNAITP) is a life-threatening bleeding disorder which results from maternal anti-platelet antibodies that cross the placenta and destroy fetal platelets. In most cases FNAITP is mediated by anti-β3 integrin antibodies, whereas reported cases of anti-GPIbα mediated FNAITP are rare. This difference can not be solely explained by the frequency of their respective polymorphisms. It is unclear whether this is due to:the GPIbα antigen being less immunogenic, resulting in less maternal antibody generation during pregnancy, oranti-GPIbα antibodies mediating a less severe pathology, resulting in a reduced number of reported cases. To study the immunogenecity and antibody response to the GPIbα antigen, GPIbα deficient mice (GPIbα−/−, Black Swiss background) were transfused with wild-type (WT) platelets. No detectable anti-GPIbα IgG antibody was induced even after 8 transfusions (108 platelets/transfusion). This clearly differs from the immune response generated in β3 integrin deficient (β3−/−, BALB/c background) mice, in which anti-β3 integrin antibody can be easily detected after 2–4 WT platelet transfusions. This suggested that the MHC complex in Black Swiss mice might not be able to present the GPIbα antigen. We thus introduced the BALB/c background to the GPIbα−/− mice via backcrossing these mice with BALB/c mice for 9 generations (F9). To further minimize genetic background differences, the F9 BALB/c GPIbα−/− mice were bred with F9 BALB/c β3−/− mice to generate heterozygous BALB/c GPIbα+/− and β3+/− mice. These mice were subsequently used to generate littermate GPIbα−/− or β3−/− mice for the following studies. We found that BALB/c GPIbα−/− mice are immunoresponsive to the GPIbα antigen, but antibody titers after 2 and 4 platelet transfusions were significantly lower than those seen with the anti-β3 integrin model (1:50 & 1:200 vs 1:400 & 1:3200 respectively, P<0.05). We then established a FNAITP model with these GPIbα−/− mice and compared it with syngeneic background β3−/− mice. Naïve (Group I) or 2-time-platelet-immunized (Group II) female GPIbα−/− or β3−/− mice were bred with WT male mice. In Group I, neonatal platelet counts after the first delivery were normal and no maternal antibody was detected for both groups. After the third delivery, GPIbα+/− pups did not have any bleeding disorders and the maternal antibody was also negative. In contrast, 14.3% of β3+/− pups were stillborn or had subcutaneous bleeding and maternal antibody was detected. In Group II, 8 pups were delivered from a GPIbα−/− female and 2 of them have minor intestinal and subcutaneous bleeding. 10 pups were delivered from 2 β3−/− female mice and 6 of them were stillborn. Of these dead pups, there was 1 case of intracranial hemorrhage and 2 immature pups. When the anti-GPIbα antibody level was increased via 4 platelet transfusions, a GPIbα−/− female had a miscarriage and severe FNAITP was observed. Our preliminary data suggested that fewer FNAITP cases reported with alloantibodies against GPIbα might not be due to the severity of FNAITP caused by this antibody, but is more likely because GPIbα is less immunogenic with a limited repertoire of MHC in pregnant women.

Maternal Immune Response to Fetal Platelet GPIbα Causes More Frequent Miscarriage in An Animal Model: A Potential Explanation for Low Reported Incidence of Fetal and Neonatal Immune Thrombocytopenia Mediated by Anti-GPIbα Antibodies.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3426-3426
Author(s):  
Conglei Li ◽  
Siavash Piran ◽  
Pingguo Chen ◽  
Sean Lang ◽  
Jerry Ware ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Titer ◽  
Immune Thrombocytopenia ◽  
Fetal Mortality ◽  
Platelet Surface ◽  
Significant Difference ◽  
Life Threatening ◽  
Β3 Integrin ◽  
Maternal Immune Response ◽  
Severe Pathology

Abstract Fetal and neonatal immune thrombocytopenia (FNIT) is a life-threatening bleeding disorder, resulting from fetal platelet opsonization and destruction by maternal antibodies developed during pregnancy. The frequency of FNIT has been estimated at 0.5–1.5/1,000 liveborn neonates. However, the incidence of fetal mortality is currently unknown, as the rate of miscarriage in affected pregnant women has not been well studied. Integrin αIIbβ3 and Glycoprotein (GP) Ibα are major glycoproteins expressed on the platelet surface and are the two major antigens targeted by anti-platelet antibodies in autoimmune thrombocytopenia (ITP). However, it is unclear why the incidence of FNIT caused by anti-GPIbα antibodies is far lower than that of FNIT mediated by anti-β3 integrin antibodies. This difference cannot be well explained by the frequency of genetic polymorphisms of the two antigens. We hypothesized that: 1) GPIbα is less immunogenic, leading to less maternal antibody production during pregnancy, or 2) anti-GPIbα antibodies cause a less severe pathology, and thus have a lower chance of being reported, or 3) anti-GPIbα antibodies cause higher incidence of miscarriage, resulting in reduced reported cases. To test these hypotheses, the maternal immune response against fetal platelet GPIbα versus β3 integrin were compared in FNIT models, using syngeneic background BALB/c GPIbα−/− and β3−/− mice. The FNIT models were established by transfusing female GPIbβ −/− or α3−/− mice with 108 gel-filtered platelets from wild-type (WT) BALB/c mice weekly. After two platelet immunizations, flow cytometry assays were used to detect the titers of anti-GPIbα and anti-β3 antibodies, and the immunized females were bred with WT BALB/c male mice. We found that there was no significant difference in mean antibody titer between the two groups (P>0.05). However, miscarriage occurred more frequently in anti-GPIbα-mediated FNIT (14/16 versus 8/16, P<0.05), particularly in pregnant mice with antibody titer less than 1:800 (11/13 versus 6/14, P<0.05). When antibody titers were higher than 1:800, miscarriage occurred in all mice and no difference was observed between the two groups (3/3 versus 2/2, P>0.05). Our data suggest that fewer reported FNIT cases mediated by anti-GPIbα antibodies cannot simply be explained by less immunogenicity of GPIbα, or less severe pathology caused by anti-GPIbα antibodies. Higher incidence of miscarriage caused by maternal immune response to fetal GPIbα likely masks the reported frequency and severity of this life-threatening disease. The mechanisms leading to miscarriage in FNIT, and the potential therapeutic effect of intravenous immunoglobulin (IVIG) in this disorder are currently being investigated. (Li C and Piran S contributed equally to this work).

scholarly journals A novel murine model of fetal and neonatal alloimmune thrombocytopenia: response to intravenous IgG therapy

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2976-2983 ◽  
Author(s):  
Heyu Ni ◽  
Pingguo Chen ◽  
Christopher M. Spring ◽  
Ebrahim Sayeh ◽  
John W. Semple ◽  
...  
Keyword(s):  
High Titer ◽  
Maternal Antibodies ◽  
Platelet Glycoprotein ◽  
Wild Type ◽  
Wild Type Male ◽  
Glycoprotein Iiia ◽  
Life Threatening ◽  
Β3 Integrin ◽  
Pathogenic Antibodies ◽  
Alloimmune Thrombocytopenia

AbstractFetal and neonatal alloimmune thrombo cytopenia (FNAITP) is a life-threatening bleeding disorder caused by maternal antibodies directed against fetal platelet antigens. The immunoreactive epitopes in FNAITP are primarily located in the extracellular regions of the platelet glycoprotein IIIa (β3 integrin). Here we have established a novel animal model of FNAITP using β3 integrin–deficient (β3-/-) mice. We demonstrated first that these mice are immunoresponsive to β3 integrin; β3-/- mice transfused with wild-type platelets generated specific anti–β3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, β3-/- female mice (both naive and immunized) were bred with wild-type male mice to recapitulate the features of FNAITP. The titer of generated maternal antibodies correlated with the severity of FNAITP. High titer maternal anti–β3 anti-bodies caused severe fetal thrombocytopenia, intracranial hemorrhage, and even miscarriage. Furthermore, maternal administration of intravenous immunoglobulin G (IgG) ameliorated FNAITP and down-regulated pathogenic antibodies in both the maternal and fetal circulations.

The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism

2004 ◽  
Vol 287 (4) ◽  
pp. R759-R766 ◽  
Author(s):  
Marie-Eve Fortier ◽  
Stephen Kent ◽  
Helen Ashdown ◽  
Stephen Poole ◽  
Patricia Boksa ◽  
...  
Keyword(s):  
Body Temperature ◽  
Viral Infections ◽  
Interleukin 1 ◽  
Male Rats ◽  
Poly I:C ◽  
Polyinosinic:Polycytidylic Acid ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Dependent Mechanism

Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded RNA that is used experimentally to model viral infections in vivo. Previous studies investigating the inflammatory properties of this agent in rodents demonstrated that it is a potent pyrogen. However, the mechanisms underlying this response have not been fully elucidated. In the current study, we examined the effects of peripheral administration of poly I:C on body temperature and cytokine production. Male rats were implanted with biotelemetry devices and randomly assigned to one of the following three groups: poly I:C + saline, poly I:C + interleukin-1 receptor antagonist (IL-1ra), or saline + saline. Maximal fever of 1.6°C above baseline was observed 3 h after an intraperitoneal injection of poly I:C (750 μg/kg). Pretreatment with IL-1ra diminished this response by >50% (maximum body temperature = 0.6°C above baseline). Plasma IL-6 concentration increased fivefold 2 h post-poly I:C compared with saline-injected rats; levels returned to baseline 4 h postinjection. Pretreatment with IL-1ra prevented this rise in IL-6. Plasma tumor necrosis factor (TNF)-α was also increased more than fourfold 2 h postinjection but remained unaffected by IL-1ra treatment. IL-1β and cyclooxygenase-2 mRNA were significantly upregulated in the hypothalamus of poly I:C-treated animals. Finally, poly I:C decreased food intake by 30%, but this response was not altered by pretreatment with IL-1ra. These results suggest that poly I:C induces fever, but not anorexia, through an IL-1 and prostaglandin-dependent mechanism.

A Review on Deadly Nipah Virus - Prevalence and its Management

2021 ◽  
pp. 2302-2307
Author(s):  
Therese Mathew ◽  
Badmanaban. R ◽  
Aby Paul ◽  
Bharat Mishra
Keyword(s):  
Viral Infections ◽  
Close Contact ◽  
Nipah Virus ◽  
System Capacity ◽  
Unknown Etiology ◽  
Surveillance Strategy ◽  
Rigorous Research ◽  
Life Threatening ◽  
Serologic Evidence ◽  
First Time

NiV is an emerging infectious disease caused by infected bats from the family of Paramyxoviridae. From its secretions the disease can be spread to humans or through close contact with infected humans. NiV was detected for the first time in 1998 in Malaysia. NiV have broad species tropism and potential that may evolve life threatening respiratory and/ or neurologic disease in humans and as well as in animals which make them important trans-boundary biological threats. The disease presented mainly as acute encephalitis with a short incubation period of less than two weeks (4 to 18 days), with the main symptoms of fever, headache and giddiness followed by coma. The major involvement of the lung and brain in NiV infection often manifested as an acute severe respiratory syndrome, encephalitis etc. In case of Henipavirus the diagnosis of infection is mainly based on the details of contact with diseased animals, evidence of encephalitis and or pneumonia, with serologic evidence of infection using Enzyme Linked Immunosorbant (EIA) assay testing or polymerase chain reaction. The anti-viral drug Ribavirin is a well-known first line treatment strategy for suspected viral infections of unknown etiology. Based on a study conducted to discover whether combining monotherapeutic treatments with Ribavirin and Chloroquine would result in any protection indicative of favourable drug-drug interactions when treatment were initiated with lethal inoculums of NiV. The reason for multiple outbreaks may be due to low healthcare system capacity and robust surveillance strategy contributes to it. Multidisciplinary and multiple facet approach is vital in preventing the emergence of NiV. It is crucial to undertake rigorous research for developing vaccines and medicines to prevent and treat NiV.

scholarly journals Immune-Mediated Control of a Dormant Neurotropic RNA Virus Infection

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Katelyn D. Miller ◽  
Christine M. Matullo ◽  
Katelynn A. Milora ◽  
Riley M. Williams ◽  
Kevin J. O’Regan ◽  
...  
Keyword(s):  
Immune Response ◽  
Protein Synthesis ◽  
Measles Virus ◽  
Viral Infections ◽  
Acute Infection ◽  
Adaptive Immune Response ◽  
Viral Control ◽  
Cns Disease ◽  
Adaptive Immune ◽  
Immune Mediated

ABSTRACTGenomic material from many neurotropic RNA viruses (e.g., measles virus [MV], West Nile virus [WNV], Sindbis virus [SV], rabies virus [RV], and influenza A virus [IAV]) remains detectable in the mouse brain parenchyma long after resolution of the acute infection. The presence of these RNAs in the absence of overt central nervous system (CNS) disease has led to the suggestion that they are viral remnants, with little or no potential to reactivate. Here we show that MV RNA remains detectable in permissive mouse neurons long after challenge with MV and, moreover, that immunosuppression can cause RNA and protein synthesis to rebound, triggering neuropathogenesis months after acute viral control. Robust recrudescence of viral transcription and protein synthesis occurs after experimental depletion of cells of the adaptive immune response and is associated with a loss of T resident memory (Trm) lymphocytes within the brain. The disease associated with loss of immune control is distinct from that seen during the acute infection: immune cell-depleted, long-term-infected mice display severe gait and motor problems, in contrast to the wasting and lethal disease that occur during acute infection of immunodeficient hosts. These results illuminate the potential consequences of noncytolytic, immune-mediated viral control in the CNS and demonstrate that what were once considered “resolved” RNA viral infections may, in fact, induce diseases later in life that are distinct from those caused by acute infection.IMPORTANCEViral infections of neurons are often not cytopathic; thus, once-infected neurons survive, and viral RNAs can be detected long after apparent viral control. These RNAs are generally considered viral fossils, unlikely to contribute to central nervous system (CNS) disease. Using a mouse model of measles virus (MV) neuronal infection, we show that MV RNA is maintained in the CNS of infected mice long after acute control and in the absence of overt disease. Viral replication is suppressed by the adaptive immune response; when these immune cells are depleted, viral protein synthesis recurs, inducing a CNS disease that is distinct from that observed during acute infection. The studies presented here provide the basis for understanding how persistent RNA infections in the CNS are controlled by the host immune response, as well as the pathogenic consequences of noncytolytic viral control.

scholarly journals Maternal Anti-Platelet β3 Integrin Antibodies Impair Angiogenesis and Cause Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2772-2772
Author(s):  
Yougbare Issaka ◽  
Sean Lang ◽  
Hong Yang ◽  
Pingguo Chen ◽  
Xu Zhao ◽  
...  
Keyword(s):  
Intracranial Hemorrhage ◽  
Network Formation ◽  
Imaging System ◽  
Conflicts Of Interest ◽  
Ivig Therapy ◽  
High Frequency Ultrasound ◽  
Akt Phosphorylation ◽  
Life Threatening ◽  
Β3 Integrin ◽  
Alloimmune Thrombocytopenia

Abstract Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease in which intracranial hemorrhage (ICH) is the major risk. Although thrombocytopenia caused by maternal antibodies against β3 integrin and occasionally against other platelet antigens (e.g. GPIbα) has long been assumed to be the cause of bleeding, the mechanism of ICH has never been adequately explored. Utilizing murine models of FNAIT and a high frequency ultrasound imaging system, we found that ICH only occurred in fetuses and neonates with anti-β3 integrin- but not anti-GPIbα-mediated FNAIT, despite similar thrombocytopenia in both groups. Only anti-β3 integrin-mediated FNAIT reduced brain and retina vessel density, impaired angiogenic signalling, and increased endothelial cell apoptosis; which were abrogated by maternal administration of intravenous immunoglobulin (IVIG). ICH and impairment of retinal angiogenesis was further reproduced in neonates by injection of anti-β3 integrin- but not anti-GPIbα-antisera. Utilizing cultured human endothelial cells, we found that cell proliferation, network formation, and Akt phosphorylation were inhibited only by murine anti-β3 integrin-antisera and human anti-HPA-1a IgG purified from mothers with FNAIT children. Our data suggest fetal hemostasis is unique in that impairment of angiogenesis rather than thrombocytopenia is likely the cause of ICH; importantly maternal IVIG therapy can effectively prevent this devastating disorder. Disclosures No relevant conflicts of interest to declare.

scholarly journals Possible harm from glucocorticoid drugs misuse in the early phase of SARS-CoV-2 infection: a narrative review of the evidence

2021 ◽  
Author(s):  
Riccardo Sarzani ◽  
Francesco Spannella ◽  
Federico Giulietti ◽  
Chiara Di Pentima ◽  
Piero Giordano ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infections ◽  
Severe Disease ◽  
Positive Outcome ◽  
Supplemental Oxygen ◽  
Time Interval ◽  
Type I ◽  
Life Threatening ◽  
The Right ◽  
Supplemental Oxygen Therapy

AbstractSince the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early. The right time interval for GC administration is still a matter of debate. Previous studies showed that an early GC use during the first phase of the disease, when viral replication peaks, may negatively affect the innate immune response through several mechanisms, such as the inhibition of pro-inflammatory and antiviral cytokine production and signaling pathway, including type I interferon, that is fundamental to counteract the virus and that was found to be impaired in several patients with life-threatening COVID-19. The GC misuse can lead to a more severe disease even in patients who do not have the established risk factors, such as obesity and cardiovascular diseases. In our focused review, we describe the role of immune response in viral infections, especially SARS-CoV-2, and discuss the potential harms of GC misuse in COVID-19.

scholarly journals Rising drug allergy alert overrides in electronic health records: an observational retrospective study of a decade of experience

2015 ◽  
Vol 23 (3) ◽  
pp. 601-608 ◽  
Author(s):  
Maxim Topaz ◽  
Diane L Seger ◽  
Sarah P Slight ◽  
Foster Goss ◽  
Kenneth Lai ◽  
...  
Keyword(s):  
Drug Allergy ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Alert Fatigue ◽  
Common Drug ◽  
Immune Mediated ◽  
Academic Hospitals ◽  
Life Threatening ◽  
The Impact ◽  
First Time

Objective There have been growing concerns about the impact of drug allergy alerts on patient safety and provider alert fatigue. The authors aimed to explore the common drug allergy alerts over the last 10 years and the reasons why providers tend to override these alerts. Design: Retrospective observational cross-sectional study (2004–2013). Materials and Methods Drug allergy alert data (n = 611,192) were collected from two large academic hospitals in Boston, MA (USA). Results Overall, the authors found an increase in the rate of drug allergy alert overrides, from 83.3% in 2004 to 87.6% in 2013 (P &lt; .001). Alarmingly, alerts for immune mediated and life threatening reactions with definite allergen and prescribed medication matches were overridden 72.8% and 74.1% of the time, respectively. However, providers were less likely to override these alerts compared to possible (cross-sensitivity) or probable (allergen group) matches (P &lt; .001). The most common drug allergy alerts were triggered by allergies to narcotics (48%) and other analgesics (6%), antibiotics (10%), and statins (2%). Only slightly more than one-third of the reactions (34.2%) were potentially immune mediated. Finally, more than half of the overrides reasons pointed to irrelevant alerts (i.e., patient has tolerated the medication before, 50.9%) and providers were significantly more likely to override repeated alerts (89.7%) rather than first time alerts (77.4%, P &lt; .001). Discussion and Conclusions These findings underline the urgent need for more efforts to provide more accurate and relevant drug allergy alerts to help reduce alert override rates and improve alert fatigue.

scholarly journals Effect of lipopolysaccharide and polyinosinic:polycytidylic acid in a murine model of nasal polyp

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jee Hye Wee ◽  
Young-Kyung Ko ◽  
Roza Khalmuratova ◽  
Hyun-Woo Shin ◽  
Dae Woo Kim ◽  
...  
Keyword(s):  
Nasal Polyp ◽  
Murine Model ◽  
Viral Infections ◽  
Poly I:C ◽  
Tissue Remodelling ◽  
Th17 Response ◽  
Cell Recruitment ◽  
Polyp Formation ◽  
Polyinosinic:Polycytidylic Acid ◽  
Recruitment Patterns

AbstractSeveral factors, including bacterial and viral infections, have been associated with rhinosinusitis and nasal tissue remodelling that may result in nasal polyp formation. However, the potential role of bacterial or viral stimuli triggering polyp development is unclear. Here, we used lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid [poly(I:C)] in a murine model of allergic rhinosinusitis to compare different effects of bacterial- and virus-derived stimuli in the pathogenesis of nasal polyp formation. Briefly, BALB/c mice were sensitised and challenged with ovalbumin and staphylococcal enterotoxin, with or without LPS or poly(I:C), and the consequent histopathological profiles, cytokines, and systemic humoral responses were studied. While no significant differences in polyp formations and epithelial disruptions were observed among the experimental groups, the local cell recruitment patterns slightly differed in animals that received either LPS or poly(I:C). Additionally, the local immune environments generated by LPS or poly(I:C) stimulation varied. LPS stimulation induced a marked Th1/Th17 response and predominantly neutrophilic nasal polyp formations, whereas poly(I:C) induced a Th2-skewed environment in neutrophilic nasal polyp development. Overall, our findings show that both cell recruitment patterns and local immune environments induced by these two stimuli differ, which may have implications in the physiopathology of rhinosinusitis with nasal polyp.

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