scholarly journals Pertussis Toxin Inhibits Early Chemokine Production To Delay Neutrophil Recruitment in Response to Bordetella pertussis Respiratory Tract Infection in Mice

2008 ◽  
Vol 76 (11) ◽  
pp. 5139-5148 ◽  
Author(s):  
Charlotte Andreasen ◽  
Nicholas H. Carbonetti
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Pertussis Toxin ◽  
Bordetella Pertussis ◽  
Inflammatory Responses ◽  
Neutrophil Migration ◽  
Neutrophil Recruitment ◽  
Chemokine Production ◽  
Neutrophil Influx

ABSTRACT Pertussis is an acute respiratory disease of humans caused by the bacterium Bordetella pertussis. Pertussis toxin (PT) plays a major role in the virulence of this pathogen, including important effects that it has soon after inoculation. Studies in our laboratory and other laboratories have indicated that PT inhibits early neutrophil influx to the lungs and airways in response to B. pertussis respiratory tract infection in mice. Previous in vitro and in vivo studies have shown that PT can affect neutrophils directly by ADP ribosylating Gi proteins associated with surface chemokine receptors, thereby inhibiting neutrophil migration in response to chemokines. However, in this study, by comparing responses to wild-type (WT) and PT-deficient strains, we found that PT has an indirect inhibitory effect on neutrophil recruitment to the airways in response to infection. Analysis of lung chemokine expression indicated that PT suppresses early neutrophil recruitment by inhibiting chemokine upregulation in alveolar macrophages and other lung cells in response to B. pertussis infection. Enhancement of early neutrophil recruitment to the airways in response to WT infection by addition of exogenous keratinocyte-derived chemokine, one of the dominant neutrophil-attracting chemokines in mice, further revealed an indirect effect of PT on neutrophil chemotaxis. Additionally, we showed that intranasal administration of PT inhibits lipopolysaccharide-induced chemokine gene expression and neutrophil recruitment to the airways, presumably by modulation of signaling through Toll-like receptor 4. Collectively, these results demonstrate how PT inhibits early inflammatory responses in the respiratory tract, which reduces neutrophil influx in response to B. pertussis infection, potentially providing an advantage to the pathogen in this interaction.

scholarly journals Pertussis Toxin Targets Airway Macrophages To Promote Bordetella pertussis Infection of the Respiratory Tract

2007 ◽  
Vol 75 (4) ◽  
pp. 1713-1720 ◽  
Author(s):  
Nicholas H. Carbonetti ◽  
Galina V. Artamonova ◽  
Nico Van Rooijen ◽  
Victor I. Ayala
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Pertussis Toxin ◽  
Bordetella Pertussis ◽  
Intranasal Administration ◽  
Protein Modification ◽  
Target Cells ◽  
Bacterial Inoculation ◽  
Enhancing Effect

ABSTRACT Pertussis toxin (PT), a secreted virulence factor of Bordetella pertussis, ADP ribosylates mammalian Gi proteins and plays an important early role in respiratory tract infection by this pathogen in a mouse intranasal infection model. To test the hypothesis that PT targets resident airway macrophages (AM) to promote this infection, we depleted AM by intranasal administration of liposome-encapsulated clodronate prior to bacterial inoculation. This treatment enhanced respiratory tract infection by B. pertussis, even though it also induced a rapid influx of neutrophils to the airways. Strikingly, AM depletion also enhanced infection by mutant strains deficient in PT production or activity to the same level as the wild-type infection, indicating that AM may be the primary target cells for PT in promoting infection. The enhancing effect of clodronate-liposome treatment on infection (i) was shown to be due to macrophage depletion rather than neutrophil influx; (ii) was observed for both tracheal infection and lung infection; (iii) was observed during the early and peak phases of the infection but was lost by day 14 postinoculation, during clearance of the infection; (iv) persisted for at least 1 week (prior to bacterial inoculation); and (v) was equivalent in magnitude to the effect of PT pretreatment and the effects were not additive, consistent with the idea that PT targets AM. We found that PT efficiently ADP ribosylated AM G proteins both in vitro and after intranasal administration of PT in mice and that the duration of G protein modification in vivo was equivalent to the duration of the enhancing effect of PT treatment on the bacterial infection. Collectively, these observations indicate that PT targets AM to promote early infection of the respiratory tract by B. pertussis.

scholarly journals Co-detection of Bordetella pertussis and other respiratory organisms in children hospitalised with lower respiratory tract infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rudzani Muloiwa ◽  
Felix S. Dube ◽  
Mark P. Nicol ◽  
Gregory D. Hussey ◽  
Heather J. Zar
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract Infection ◽  
Bordetella Pertussis ◽  
Lower Respiratory Tract ◽  
Vaccine Coverage ◽  
Adjusted Risk ◽  
Increased Risk ◽  
Co Detection

Abstract Multiple potential pathogens are frequently co-detected among children with lower respiratory tract infection (LRTI). Evidence indicates that Bordetella pertussis has an important role in the aetiology of LRTI. We aimed to study the association between B. pertussis and other respiratory pathogens in children hospitalised with severe LRTI, and to assess clinical relevance of co-detection. Nasopharyngeal (NP) swabs and induced sputa (IS) were tested with a B. pertussis specific PCR; additionally, IS was tested for other pathogens using a multiplex PCR. We included 454 children, median age 8 months (IQR 4–18), 31 (7%) of whom tested positive for B. pertussis. Children with B. pertussis had more bacterial pathogens detected (3 versus 2; P < 0.001). While B. pertussis showed no association with most pathogens, it was independently associated with Chlamydia pneumoniae, Mycoplasma pneumoniae and parainfluenza viruses with adjusted risk ratios of 4.01 (1.03–15.64), 4.17 (1.42–12.27) and 2.13 (1.03–4.55), respectively. There was a consistent increased risk of severe disease with B. pertussis. Patterns indicated even higher risks when B. pertussis was co-detected with any of the three organisms although not statistically significant. Improving vaccine coverage against B. pertussis would impact not only the incidence of pertussis but also that of severe LRTI generally.

scholarly journals Sex differences in the immune response to acute COVID-19 respiratory tract infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shaohua Qi ◽  
Conelius Ngwa ◽  
Diego A. Morales Scheihing ◽  
Abdullah Al Mamun ◽  
Hilda W. Ahnstedt ◽  
...  
Keyword(s):  
Immune Response ◽  
Sex Differences ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Hospitalized Patients ◽  
Severe Illness ◽  
Control Group

Abstract Background Sex differences in COVID-19 are increasingly recognized globally. Although infection rates are similar between the sexes, men have more severe illness. The mechanism underlying these sex differences is unknown, but a differential immune response to COVID-19 has been implicated in several recent studies. However, how sex differences shape the immune response to COVID-19 remains understudied. Methods We collected demographics and blood samples from over 600 hospitalized patients diagnosed with COVID-19 from May 24th 2020 to April 28th, 2021. These patients were divided into two cohorts: Cohort 1 was further classified into three groups based on the severity of the disease (mild, moderate and severe); Cohort 2 patients were longitudinally followed at three time points from hospital admission (1 day, 7 days, and 14 days). MultiPlex and conventional ELISA were used to examine inflammatory mediator levels in the plasma in both cohorts. Flow cytometry was conducted to examine leukocyte responses in Cohort 2. Results There were more COVID+ males in the total cohort, and the mortality rate was higher in males vs. females. More male patients were seen in most age groups (in 10-year increments), and in most ethnic groups. Males with severe disease had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-8, MCP-1) than females; levels of IL-8, GRO, sCD40L, MIP-1β, MCP-1 were also significantly higher in severe vs. mild or control patients in males but not in females. Females had significantly higher anti-inflammatory cytokine IL-10 levels at 14 days compared to males, and the level of IL-10 significantly increased in moderate vs. the control group in females but not in males. At 7 days and 14 days, males had significantly more circulating neutrophils and monocytes than females; however, B cell numbers were significantly higher in females vs. males. Conclusion Sex differences exist in hospitalized patients with acute COVID-19 respiratory tract infection. Exacerbated inflammatory responses were seen in male vs. female patients, even when matched for disease severity. Males appear to have a more robust innate immune response, and females mount a stronger adaptive immune response to COVID-19 respiratory tract infection.

scholarly journals Suppression of Serum Antibody Responses by Pertussis Toxin after Respiratory Tract Colonization by Bordetella pertussis and Identification of an Immunodominant Lipoprotein

2004 ◽  
Vol 72 (6) ◽  
pp. 3350-3358 ◽  
Author(s):  
Nicholas H. Carbonetti ◽  
Galina V. Artamonova ◽  
Charlotte Andreasen ◽  
Edward Dudley ◽  
R. Michael Mays ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Tract Infection ◽  
Antibody Response ◽  
Respiratory Tract ◽  
Pertussis Toxin ◽  
Bordetella Pertussis ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Low Molecular Weight ◽  
Respiratory Tract Colonization

ABSTRACT Pertussis toxin (PT), a virulence factor secreted by Bordetella pertussis, contributes to respiratory tract infection and disease caused by this pathogen. By comparing a wild-type (WT) B. pertussis strain to a mutant strain with an in-frame deletion of the ptx genes encoding PT (ΔPT), we recently found that the lack of PT confers a significant defect in respiratory tract colonization in mice after intranasal inoculation. In this study, we analyzed serum antibody responses in mice infected with the WT or ΔPT strain and found that infection with the ΔPT strain elicited greater responses to several B. pertussis antigens than did infection with the WT, despite the lower colonization level achieved by the ΔPT strain. The same enhanced antibody response was observed after infection with a strain expressing an enzymatically inactive PT; but this response was not observed after infection with B. pertussis mutant strains lacking filamentous hemagglutinin or adenylate cyclase toxin, nor when purified PT was administered with the ΔPT inoculum, indicating a specific role for PT activity in this immunosuppressive effect. In particular, there were consistent strong serum antibody responses to one or more low-molecular-weight antigens after infection with the ΔPT strain. These antigens were Bvg independent, membrane localized, and also expressed by the closely related pathogens Bordetella parapertussis and Bordetella bronchiseptica. Two-dimensional gel electrophoresis and mass spectrometry were used to identify one of the immunodominant low-molecular-weight antigens as a protein with significant sequence homology to peptidoglycan-associated lipoprotein in several other gram-negative bacterial species. However, a serum antibody response to this protein alone did not protect mice against respiratory tract infection by B. pertussis.

Antibiotic consumption and susceptibility of isolates in patients with low respiratory tract infection

Pneumologie ◽  
2015 ◽  
Vol 69 (S 01) ◽  
Author(s):  
EJS Hurtado ◽  
MJG Fernández ◽  
AA Arregosa ◽  
JM González Miret ◽  
MZ Rascón ◽  
...  
Keyword(s):  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Antibiotic Consumption
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