Chlamydia Pneumoniae Infection Research Articles

Chlamydia pneumonia infection and risk of multiple sclerosis: A meta-analysis.

The role of infectious agents, including Chlamydia pneumoniae (Cpn), in the development of multiple sclerosis (MS), is still a matter of major contention. This meta-analysis study aimed to assess the actual involvement of Cpn in MS development. We undertook a search of international scientific databases to identify eligible studies. We used a random-effects meta-analysis model (REM) to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Heterogeneity was calculated using the I2 statistic. Sensitivity and subgroup analyses were applied to assess the effects of study characteristics and socio-demographic variables on the pooled OR. We identified 37 studies comprising 51 datasets that satisfied the inclusion criteria. Considering diagnostic methods for Cpn, 26 and 25 datasets used PCR- and serological-based methods, respectively. In PCR-based datasets, REM showed a significant positive association between Cpn infection and the development of MS (OR, 5.29; 95% CI, 3.12-8.97), while a non-significant positive association was achieved in serological-based datasets (OR, 1.34; 95% CI, 0.88-2.03). In subgroup analyses on PCR-based datasets, results were significant for both CSF (OR, 5.70) and serum (OR, 4.84) samples; both healthy (OR, 16.11) and hospital-based (OR, 2.88) controls; and both moderate (OR, 5.14) and high (OR, 5.48) quality studies. In serological-based datasets, only those that used CSF samples yielded significant results (OR, 3.41). Our findings verify the significant positive relationship between Cpn infection and MS. We advocate prospective cohort studies with lifelong follow-ups and also experimental studies to better understand the role of Cpn in MS development.

Chronic Chlamydia pneumonia Infection and Risk of Early-Onset Versus Late-Onset Preeclampsia.

Preeclampsia is one of the challenges associated with mother and baby health. Preeclampsia and atherosclerosis share certain similarities. Atherosclerosis has been previously linked to chronic Chlamydia pneumoniae infection. This investigation aimed to establish the role of chronic Chlamydia pneumoniae in the development and onset of preeclampsia. The research was conducted from October 1, 2018 to September 30, 2019 in the department of Obstetrics and Gynecology at Al-Yarmouk Teaching Hospital in Baghdad, Iraq. The study included 140 pregnant women divided into two groups: 70 women with early and late-onset preeclampsia and 70 women with late-onset preeclampsia. Group I (early-onset preeclampsia) included 35 singleton pregnant women who developed preeclampsia after 34 weeks with blood pressure>140/90 and proteinuria>1. Late-onset preeclampsia (group II) consisted of 35 singleton pregnant women who developed clinical preeclampsia after 34 weeks of pregnancy, with blood pressure>140/90 and proteinuria +1, and 70 healthy term pregnant women without complications who acted as the control group (Group III). Enzyme-Linked Immunosorbent Assay (ELISA) analyzers were utilized to measure serum Chlamydia pneumoniae IgG levels in all study groups. Women with early-onset preeclampsia had the highest median Chlamydia pneumonia IgG level, 0.3 U/ml, compared to 0.09 U/ml for women with late-onset preeclampsia and 0.19U/ml for healthy term pregnant women without complications; these differences were statistically significant (P=0.001). This study found that the IgG titer for Chlamydia pneumoniae was higher in early-onset preeclampsia than in late-onset preeclampsia and in healthy term pregnancy without complications. This substantial increase was a direct result of the onset of preeclampsia. This provided evidence for the pathophysiological connection between preeclampsia and the reactivation of a chronic or latent infection.

Association between infection with Chlamydia pneumonia and cerebral noncardioembolic ischemic stroke

Introduction: Stroke is the third most common cause of mortality and the most common disability disorder among adults. We aimed to study the relationship between Chlamydia pneumonia infection and non-cardio Ambulatory ischemic stroke.Methods: This case-control study was performed on 162 patients with non-cardio ambulatory ischemic stroke admitted to Shahid Beheshti Hospital of Kashan in 2019 as the case group and patients with neurological headache and degenerative diseases as the control group. After filling out the questionnaire for all subjects, we took blood samples. We analyzed all three anti-chlamydia pneumonia antibodies (IgM, IgG, IgA) by ELISA method after data were analyzed by Chi-square and Fisher tests.Results: The findings of this study showed that positive IgA in the stroke group was significantly higher than in the control group (p=0.001); it was also found that the risk factors of HTN (p=0.001), HLP (p=0.001), DM (p=0.001), and age (p = 0.049) were significantly higher in the stroke patients’ group than the control group. On the other hand, there was not a significant difference in serum IgG level (p = 0.349), IgM (p = 0.745), smoking (p = 0.211) and gender (p = 0.157) in understudied groups.Conclusion: Chlamydia IgA antibodies can be a complementary tool for predicting prognosis and monitoring new therapies for ischemic stroke. This study provides a way for further studies, especially with other markers of acute and chronic systemic Chlamydia pneumonia infection. Antibiotic treatment significantly helps to reduce mortality and stroke complications.

Epidemiological Study on Mycoplasma pneumoniae and Chlamydia pneumoniae Infection of Hospitalized Children in a Single Center During the COVID-19 Pandemic.

BackgroundSince the outbreak of COVID-19, a series of preventive and control measures in China have been used to effectively curb the spread of COVID-19. This study aimed to analyze the epidemiological characteristics of Mycoplasma pneumoniae (MP) and Chlamydia pneumoniae (CP) in hospitalized children with acute respiratory tract infection during the COVID-19 pandemic.Methods MP IgM antibody and CP IgM antibody were detected in all hospitalized children due to acute respiratory tract infection in the Children’s Hospital Affiliated to Zhejiang University from January 2019 to December 2020. These data were compared between 2019 and 2020 based on age and month.ResultsThe overall detection rate of MP and CP in 2020 was significantly lower than that in 2019 (MP: 21.5% vs 32.9%, P<0.001; CP: 0.3% vs 0.9%, P<0.001). This study found a 4-fold reduction in the number of children positive for MP and a 7.5-fold reduction in the number of children positive for CP from 2019 to 2020. The positive cases were concentrated in children aged >1 year old. In 2019, the positive rate of MP was detected more commonly in children 3 years of age or older than in younger children. In 2020, the higher positive rate of MP reached a peak in the 3- to 6-year age group (35.3%). CP was detected predominantly in children aged 6 years older in 2019 and 2020, with positive rates of 4.8% and 2.6%, respectively. Meanwhile, the positive rates of MP in 2019 were detected more commonly in July, August and September, with 47.2%, 46.7% and 46.3%, respectively. Nevertheless, the positive rates of MP from February to December 2020 apparently decreased compared to those in 2019. The positive rates of CP were evenly distributed throughout the year, with 0.5%-1.6% in 2019 and 0.0%-2.1% in 2020.ConclusionsA series of preventive and control measures for SARS-CoV-2 during the COVID-19 pandemic can not only contain the spread of SARS-CoV-2 but also sharply improve the infection of other atypical pathogens, including MP and CP.

Association Between Antibiotic Treatment of Chlamydia pneumoniae and Reduced Risk of Alzheimer Dementia: A Nationwide Cohort Study in Taiwan.

Background:Chlamydia pneumoniae (CPn) is a common community-acquired pneumonia. In the literature, CPn infection is demonstrated to exhibit an association with Alzheimer dementia (AD). We executed the present nationwide, population-based research with the goal of probing the association of CPn infection and antibiotic therapy with AD risk.Methods: We conducted a cohort study using a database extracted from Taiwan's National Health Insurance Research Database (NHIRD). All medical conditions for each enrolled individuals were categorized using the International Classification of Diseases, ninth Revision classifications. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CPn pneumonia-associated hospitalizations and AD were estimated using Fine and Gray's survival analysis and adjusted for comorbidities. The effects of the antibiotics on the HRs for AD in the patients with CPn pneumonia-associated hospitalization were also analyzed.Results: Our analyses included 6,628 individuals, including 1,657 CPn-infected patients, as well as 4,971 controls matched by age, index date, and sex (1:3). In this study, patients hospitalized for CPn pneumonia exhibited a significantly higher AD risk (adjusted HR = 1.599, 95% CI = 1.284–1.971, p < 0.001). We also noted an association of macrolide use (≥15 days) and fluoroquinolone use (≥15 days) with decreased AD risk.Conclusions: We determined CPn pneumonia to be associated with a relatively high AD risk. The result in this study confirmed the findings from previous literatures, by using a large, nationwide, population-based database. Appropriate macrolide and fluoroquinolone treatment may attenuate this risk.

Seroepidemiology Study of Helicobacter pylori Infection and Its Effect on Cardiovascular Diseases in Karaj, Iran.

Helicobacter pylori infection occurs throughout the world between countries and races. A seroprevalence study of H. pylori infection in the occurrence of atherosclerosis (ASc) has been considered to be the main cause of cardiovascular diseases (CVDs) in part of Iran. From 600 volunteers, 97 serum samples were selected and tested for the presence of H. pylori infection. Positive and negative H. pylori infection samples were then selected for Chlamydia pneumonia and cytomegalovirus infection. Their serum levels for high-sensitive C-reactive protein (hs-CRP) and IL-6 titer were measured using an ELISA test. Prevalence of H. pylori infection was ∼68.04% in Karaj. Among the 22 samples of cytokine titration, 4 individuals were HP- and 18 were HP+. It was also noticed that 17 samples had normal titration (77.27%) of IL-6 and 3 had a high level of IL-6 (13.63%), 20 people had high hs-CRP titration (90.90%), and 2 were low level hs-CRP (9.1%). Obtained results showed that there is no significant difference between HP+ and HP- infection and IL-6 and hs-CRP titration. Results showed that H. pylori could not lead to ASc by increasing the levels of proinflammatory cytokines such as IL-6 and hs-CRP. Further studies are necessary for the detection of mechanism of H. pylori on ASc.

Genome-wide DNA methylation and RNA expression profiles identified RIPK3 as a differentially methylated gene in Chlamydia pneumoniae infection lung carcinoma patients in China.

Aim: To explore the relationship between Chlamydia pneumonia (Cpn) infection and lung cancer using integrative methylome and transcriptome analyses.Methods: Twelve primary lung cancer patients who were positive for Cpn and twelve patients who were negative were selected for demographic, clinicopathological, and lifestyle matching. Genomic DNA and RNA were extracted and DNA methylation and mRNA levels were detected using the Infinium Human Methylation 450 Beadchip array and mRNA + lncRNA Human Gene Expression Microarray. We identified differentially expressed methylation and genes profiles.Results: Integrative analysis revealed an inverse correlation between differentially expressed genes and DNA methylation. Cpn-related lung cancer methylated genes (target genes) were introduced into the gene ontology and KEGG, PID, BioCarta, Reactome, BioCyc and PANTHER enrichment analyses using a q-value cutoff of 0.05 to identify potentially functional methylation of abnormal genes associated with Cpn infection. Gene sets enrichment analysis was evaluated according to MsigDB. Levels of differentially expressed methylated sites were quantitatively verified. The promoter methylation sites of 62 genes were inversely related to expression levels. According to the quantitative analysis of DNA methylation, the methylation level of the RIPK3 promoter region was significantly different between Cpn-positive cancerous and adjacent tissues, but not between Cpn-negative cancerous and adjacent tissues.Conclusion: Hypomethylation of the RIPK3 promoter region increases RIPK3 expression, leading to regulated programmed necrosis and activation of NF-κB transcription factors, which may contribute to the development and progression of Cpn-related lung cancer.

Autophagy Limits Inflammasome During Chlamydia pneumoniae Infection.

Autophagy can either antagonize or promote intracellular bacterial growth, depending on the pathogen. Here, we investigated the role of autophagy during a pulmonary infection with the obligate intracellular pathogen, Chlamydia pneumoniae (CP). In mouse embryonic fibroblasts (MEFs) or macrophages, deficiency of autophagy pathway components led to enhanced CP replication, suggesting that autophagy exerts a bactericidal role. However, in vivo, mice with myeloid-specific deletion of the autophagic protein ATG16L1 suffered increased mortality during CP infection, neutrophilia, and increased inflammasome activation despite no change in bacterial burden. Induction of autophagy led to reduced CP replication in vitro, but impaired survival in CP-infected mice, associated with an initial reduction in IL-1β production, followed by enhanced neutrophil recruitment, defective CP clearance, and later inflammasome activation and IL-1β production, which drove the resulting mortality. Taken together, our data suggest that a delicate interplay exists between autophagy and inflammasome activation in determining the outcome of CP infection, perturbation of which can result in inflammatory pathology or unrestricted bacterial growth.

Bacterial infections are associated with cardiovascular disease in Iran: a meta-analysis.

IntroductionThe present study aimed to assess the prevalence and association of various bacterial infections with cardiovascular disease (CVD) in Iran.Material and methodsAn electronic search was performed using related keywords in the national and international databases up to June 30, 2017. Out of the 1807 articles found on the associations between bacterial infections and CVD, 20 relevant studies were selected for the meta-analysis.ResultsThe prevalence of bacterial infections was higher in case groups compared with the control groups. Odds ratios for assessing the association between Chlamydia pneumonia infection and CVD based on PCR, IgG and IgA tests were 7.420 (95% CI: 3.088–17.827), 3.710 (95% CI: 1.361–10.115) and 2.492 (95% CI: 1.305–4.756), respectively. Moreover, the calculated odds ratio for Mycoplasma pneumonia infection was 1.815 (95% CI: 0.973–3.386). For Helicobacter pylori infection, odds ratios based on IgG and IgA tests were 3.160 (95% CI: 1.957–5.102) and 0.643 (95% CI: 0.414–0.999), respectively.ConclusionsThe present meta-analysis suggested that there was a significant association between H. pylori, C. pneumonia and M. pneumonia infections and CVD in Iran. These findings confirm the potential role of bacterial infections as predisposing factors for CVD.

Tumor necrosis factor receptor superfamily members 1a and 1b contribute to exacerbation of atherosclerosis by Chlamydia pneumoniae in mice

The host immune responses that mediate Chlamydia-induced chronic disease sequelae are incompletely understood. The role of TNF-α, TNF receptor 1 (TNFR1), and TNF receptor 2 (TNFR2), in Chlamydia pneumoniae (CPN)-induced atherosclerosis was studied using the high-fat diet-fed male C57BL/6J mouse model. Following intranasal CPN infection, TNF-α knockout (KO), TNFR1 KO, TNFR2 KO, and TNFR 1/2 double-knockout, displayed comparable serum anti-chlamydial antibody response, splenic antigen-specific cytokine response, and serum cholesterol profiles compared to wild type (WT) animals. However, atherosclerotic pathology in each CPN-infected KO mouse group was reduced significantly compared to WT mice, suggesting that both TNFR1 and TNFR2 promote CPN-induced atherosclerosis.

Serological Analysis and Drug Resistance of Chlamydia pneumoniae and Mycoplasma pneumoniae in 4500 Healthy Subjects in Shenzhen, China.

Objective To understand the prevalence and distribution of Chlamydia pneumoniae (CP) and Mycoplasma pneumoniae (MP) in the population and to provide a basis for the prevention and treatment of respiratory tract infection. Methods This study included a total of 4500 healthy subjects who were given physical examination in Shenzhen People's Hospital from January to December in 2016. Venous blood was drawn from people to detect the MP- and CP-specific IgG and IgM in the serum using chemiluminescence immunoassay (CLIA). The relationship of MP and CP infections with patient age, seasons, and percentage of infections was analyzed. Conclusion CP and MP cause high rate of asymptomatic infection, which may be associated with the high incidence of CP and MP infection, especially in children and the elderly population. Therefore, the implementation of effective and practical prevention measures has become an urgent need. MP culture and drug sensitivity test should be performed as early as possible in patients with manifested MP infections in order to ensure timely and proper treatment and to reduce the emergence of drug-resistant strains.

Chlamydia Pneumoniae and Acute Aortic Syndrome: A Call for a Multi-Institutional Study

Chlamydia Pneumoniae (CP) infection is strongly associated with coronary artery disease, as well as with atherosclerosis of the carotid and peripheral arteries. However, the role of CP in the pathogenesis of aortic disease remains controversial. Our present experience suggests no correlation between a current infection with C. pneumoniae and acute aortic dissection. Well-designed large prospective studies are needed in order to clarify the pathophysiologic role of CP infection in acute and chronic aortic disease.

Detection of Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila in children with acute respiratory infection

Objective To analyze the characteristics of Mycoplasma pneumo-niae(MP), Chlamydia pneumo-niae (CP), Legionella pneumophila (LP) in hospitalized children with acute respiratory tract infection. Methods Serum and urine were collected from 5275 children (aged from 3 days to 16 years old) admitted with acute respiratory tract infection from Jan. to Dce. 2012. The levels of MP-IgM, CP-IgM in serum, and LP antigen in urine were detected by passive agglutination, enzyme-linked immunosorbent assay, and immunochromatographic assay respectively. The epidemiology of positive cases were analyzed. Results 1. Among 5275 children with acute respiratory tract infection, 1537 cases (29.1%) were detected with at least 1 type of the pathogens: MP infection was 20.1% (1060 cases), CP infection was 8.7%(45 cases), and LP positive rate was 0.3%(18 cases), mix infection rate was 2.56%(135 cases).2. The prevalence of MP, CP and LP infections in the different months and quarters were significantly different(all P<0.01). The positive rate of MP was highest in November while it was lowest in May. The positive rate of CP was highest in November while it was lowest in July. The positive rate of LP was highest in December, no infection case was found in February, May and the time during July to November.3. In all, the occurrence of positive results of MP, CP, and LP in children were higher in winter than that in other seasons. The infection of December was more than that in the other month. Meanwhile, infection of MP, CP and LP were mostly occured in children over age of 5. In addition, the positive rates were higher in male than that in female. Furthermore, children with bronchial pneumonia had higher positive rates of infection compared to children with acute respiratory tract infection. Conclusion Pathogen detection is an important basis for the diagnosis of children with the infection of MP, CP, LP. Key words: Acute respiratory tract infection; Mycoplasma pneumoniae; Chlamydia pneumoniae; Legionella pneumophila; Child

Chlamydia pneumoniae Infection in Mice Induces Chronic Lung Inflammation, iBALT Formation, and Fibrosis

Chlamydia pneumoniae (CP) lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chronic changes in the lungs. We infected C57BL/6 mice with 5×105 CP intratracheally and monitored inflammation, cellular infiltrates and cytokine levels over time to investigate the chronic inflammatory lung changes. While bacteria numbers declined by day 28, macrophage numbers remained high through day 35. Immune cell clusters were detected as early as day 14 and persisted through day 35, and stained positive for B, T, and follicular dendritic cells, indicating these clusters were inducible bronchus associated lymphoid tissues (iBALTs). Classically activated inflammatory M1 macrophages were the predominant subtype early on while alternatively activated M2 macrophages increased later during infection. Adoptive transfer of M1 but not M2 macrophages intratracheally 1 week after infection resulted in greater lung inflammation, severe fibrosis, and increased numbers of iBALTS 35 days after infection. In summary, we show that CP lung infection in mice induces chronic inflammatory changes including iBALT formations as well as fibrosis. These observations suggest that the M1 macrophages, which are part of the normal response to clear acute C. pneumoniae lung infection, result in an enhanced acute response when present in excess numbers, with greater inflammation, tissue injury, and severe fibrosis.

Plasmacytoid Dendritic Cells Play a Role for Effective Innate Immune Responses during Chlamydia pneumoniae Infection in Mice

Plasmacytoid dendritic cells (pDCs) are known for their robust antiviral response and their pro-tolerance effects towards allergic diseases and tissue engraftments. However, little is known about the role pDCs may play during a bacterial infection, including pulmonary Chlamydia pneumoniae (CP). In this study, we investigated the role of pDCs during pulmonary CP infection. Our results revealed that depletion of pDCs during acute CP infection in mice results in delayed and reduced lung inflammation, with an early delay in cellular recruitment and significant reduction in early cytokine production in the lungs. This was followed by impaired and delayed bacterial clearance from the lungs which then resulted in a severe and prolonged chronic inflammation and iBALT like structures containing large numbers of B and T cells in these animals. We also observed that increasing the pDC numbers in the lung by FLT3L treatment experimentally results in greater lung inflammation during acute CP infection. In contrast to these results, restimulation of T-cells in the draining lymph nodes of pDC-depleted mice induced greater amounts of proinflammatory cytokines than we observed in control mice. These results suggest that pDCs in the lung may provide critical proinflammatory innate immune responses in response to CP infection, but are suppressive towards adaptive immune responses in the lymph node. Thus pDCs in the lung and the draining lymph node appear to have different roles and phenotypes during acute CP infection and may play a role in host immune responses.

Distinct genetic and infectious profiles in Japanese neuromyelitis optica patients according to anti-aquaporin 4 antibody status

ObjectiveTo clarify whether genetic and common infectious backgrounds are distinct, according to anti-aquaporin 4 (AQP4) antibody status in Japanese patients with neuromyelitis optica (NMO).MethodsWe analysed human leucocyte antigen (HLA)-DRB1 and...

Chlamydia Pneumoniae Infection Associated with Uncontrolled Asthma: A Hospital Based Cross Sectional Study

To evaluate the proportion of anti- Chlamydia pneumoniae (Cp) IgM positivity in patients with uncontrolled asthma and partly controlled childhood asthma and their clinical correlates. This was a hospital based cross sectional study. Children aged 1 to 12 y suffering from asthma were included after written informed parental consent. For diagnosis and classification of uncontrolled and partly controlled asthma, GINA guidelines 2009 were used. Anti-Cp IgM was tested by using an enzyme linked immunosorbent assay (ELISA) and value of antibody index ≥ 0.90 was considered positive. Data was collected on demographic, clinical and investigative variables including chest radiograph posterior-anterior view. From August 2010 through August 2011 44 patients hospitalized with uncontrolled asthma in exacerbation and 45 patients with partly controlled asthma from ambulatory care settings were included. Anti-Cp IgM was positive in 25 % (n = 11/44) and 6.7 % (n = 3/45) patients with uncontrolled and partly controlled asthma, respectively (Odds ratio = 4.67, χ (2) = 5.64, 95 % CI 1.20-18.10, p 0.0 17). Among the patients of uncontrolled asthma, duration of hospital stay was longer in anti-Cp IgM positive patients (9 ± 2.19 vs. 7.19 ± 2.10 d, p 0.02). Since anti-Cp IgM positivity was associated with age >5 y and radiological consolidation in uncontrolled asthma in exacerbation, specific treatment of Chlamydia pneumoniae must be actively considered.

Relationship of cytomegalovirus, Chlamydia pneumoniae and herpes simplex virus type 2 infections with preeclampsia

To explore the potential relationship of cytomegalovirus (CMV), Chlamydia pneumoniae (CP) and herpes simplex virus type 2 (HSV-2) in inflammation and preeclampsia. Fifty-two pregnant women with preeclampsia and 34 with uncomplicated pregnancy in the third trimester were recruited. The exclusions included uterine contractions, multiple pregnancies, rupture of membranes, symptomatic infectious diseases, medical diseases and antibiotics or hormones users. Samples of maternal blood were harvested from two groups. Serum levels of CMV, CP, and HSV-2 IgM and IgG antibodies as well as high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA) in preeclampsia and normal pregnancy controls. (1) Recent infections of CMV, CP and HSV-2 were not more common in patients with preeclampsia versus normal pregnancy. The prevalence rates of long-dated CMV, CP and HSV-2 infection were 94.2% (49/52), 53.9% (28/52) and 3.9% (2/52) in preeclampsia group versus 100.0% (34/34), 55.9% (19/34) and 5.9% (2/34) in control group. No significant difference existed between two groups (P > 0.05). (2) Maternal serum concentrations of IL-6 and hs-CRP in patients with preeclampsia were significantly higher than that in normal pregnancy women ((7.2 ± 2.1) ng/L and (6.8 ± 5.6) mg/L vs (6.2 ± 1.8) ng/L and (4.6 ± 3.0) mg/L, both P < 0.05). Excessive inflammatory reactions are present in women with preeclampsia. But previous infections, as measured by IgM and IgG antibody seropositivity to CMV, CP and HSV-2, are not correlated with preeclampsia in the third trimester.

Caspase-1 Dependent IL-1β Secretion Is Critical for Host Defense in a Mouse Model of Chlamydia pneumoniae Lung Infection

Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the ‘inflammasome’, and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1−/− mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1−/− mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice phenocopies Caspase-1-deficient mice, and administration of recombinant IL-1β rescues CP infected Caspase-1−/− mice from mortality, indicating that IL-1β secretion is crucial for host immune defense against CP lung infection. In vitro investigation reveals that CP-induced IL-1β secretion by macrophages requires TLR2/MyD88 and NLRP3/ASC/Caspase-1 signaling. Entry into the cell by CP and new protein synthesis by CP are required for inflammasome activation. Neither ROS nor cathepsin was required for CP infection induced inflammasome activation. Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation.

Chlamydia pneumoniae Infection Induced Allergic Airway Sensitization Is Controlled by Regulatory T-Cells and Plasmacytoid Dendritic Cells

Chlamydia pneumoniae (CP) is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate), but not a high dose (severe) CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2−/−, and TLR4−/− mice were infected intranasally (i.n.) with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA) and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2−/− mice, but not in TLR4−/− mice, due to differential Treg responses in these genotypes. TLR2−/− mice had reduced numbers of Tregs in the lung during CP infection while TLR4−/− mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs.