Background
Pertussis, commonly known as whooping cough, is a highly contagious respiratory illness caused by the bacterium Bordetella pertussis. Early symptoms in patients are relatively mild, usually manifesting as coughing, sneezing, and low fever. As the infection progresses, patients may experience severe coughing fits that can be paroxysmal and spasmodic. Bordetella pertussis is specific to humans and is a specialized aerobic coccobacillus. Several virulence factors secreted by Bordetella pertussis contribute to the development of pertussis, including pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and lipopolysaccharide (LPS), which play an important role in its pathogenicity and immune response, and produce varying degrees of damage to the host immune system. Current classification of Bordetella pertussis is based on its surface antigens. with the main classification systems being PT, FHA and PRN. Among these, the PRN classification divides strains into PRN-1, PRN-2, and PRN-3, with PRN-1 being the most prevalent.
Bordetella pertussis predominantly infects the respiratory tract and is transmitted through respiratory droplets from individuals who are infected. After inhalation, B. pertussis enters the upper respiratory tract and attaches to the epithelial cells of the nasopharynx and trachea. Upon attachment to these cells, B. pertussis begins to produce various virulence factors, including adhesins, immunomodulators, and toxins. These factors are crucial for the bacterium's survival, as they hinder its rapid clearance from the host's immune system and facilitate its progression into the lower respiratory tract. Once it binds to host cell receptors, B. pertussis further expresses key virulence factors such as FHA and PRN. The presence of these factors not only aids in maintaining the infection but also contributes to the disease's characteristic symptoms by disrupting normal respiratory function.
Figure 1. Schematic figure of B. pertussis and its virulence factors
(Source: Zlamy M. 2016)
Pertussis is now considered the most common vaccine-preventable disease. The incidence of pertussis declined significantly in the 20th century following the large-scale application of the diphtheria-tetanus-pertussis (DTP) vaccine, which was prepared by combining inactivated B. pertussis with diphtheria toxoid and tetanus toxoid. Initially the pertussis vaccine was vaccinated with whole-cell pertussis (wP) vaccine, but it has been associated with serious adverse events related to pertussis and even deaths of the vaccinated individuals. Subsequent development of an acellular pertussis vaccine (aP) was more immunogenic and safer. Nonetheless, there is a tendency for pertussis to return, with a significant increase in incidence in some parts of the country. The researchers found that the recurrent prevalence of pertussis existed before aP was applied, but the use of DTaP accelerated the trend. The aP vaccine produces immunity that decays rapidly and has a low memory immune response compared to wP. DTaP is a Th2 type of immunity that predominantly induces humoral immunity, whereas DTwP is primarily a Th1 type of immunity that induces cellular immunity.
Alternative Names
B. pertussis Lipopolysaccharide
References
- 1. Kilgore PE, et al. Pertussis: Microbiology, Disease, Treatment, and Prevention. Clin Microbiol Rev. 2016 Jul;29(3):449-86.
- 2. Zlamy M. Rediscovering Pertussis. Front Pediatr. 2016 Jun 8;4:52.
References
The modulatory effects of lipopolysaccharide-stimulated B cells on differential T-cell polarization
IMMUNOLOGY
Authors: Xu, Hui; Liew, Lip Nyin; Kuo, I. Chun; Huang, Chiung Hui; Goh, Denise Li-Meng; Chua, Kaw Yan
Abstract
Lipopolysaccharide (LPS) is a major component of environmental microbial products. Studies have defined the LPS dose as a critical determining factor in driving differential T-cell polarization but the direct effects of LPS on individual antigen-presenting cells is unknown. Here, we investigated the effects of LPS doses on naive B cells and the subsequent modulatory effects of these LPS-activated B cells on T-cell polarization. The LPS was able to induce a proliferative response starting at a dose of 100 ng/ml and was capable of enhancing antigen internalization at a dose of 1 mu g/ml in naive B cells. Following LPS stimulation, up-regulation of the surface markers CD40, CD86, I-A(d), immunoglobulin M, CD54 and interleukin-10 production, accompanied by down-regulation of CD5 and CD184 (CXCR4) were observed in a LPS dose-dependent manner. Low doses (< 10 ng/ml) of LPS-activated B cells drove T helper type 2 polarization whereas high doses (> 0.1 mu g/ml) of LPS-activated B cells resulted in T regulatory type 1 cell polarization. In conclusion, LPS-activated B cells acquire differential modulatory effects on T-cell polarization. Such modulatory effects of B cells are dependent on the stimulation with LPS in a dose-dependent manner. These observations may provide one of the mechanistic explanations for the influence of environmental microbes on the development of allergic diseases.
Serum amyloid A mediates human neutrophil production of reactive oxygen species through a receptor independent of formyl peptide receptor like-1
JOURNAL OF LEUKOCYTE BIOLOGY
Authors: Bjoerkman, Lena; Karlsson, Jennie; Karlsson, Anna; Rabiet, Marie-Josephe; Boulay, Francois; Fu, Huamei; Bylund, Johan; Dahlgren, Claes
Abstract
Serum amyloid A (SAA) is one of the acute-phase reactants, a group of plasma proteins that increases immensely in concentration during microbial infections and inflammatory conditions, and a close relationship between SAA levels and disease activity in rheumatoid arthritis (RA) has been observed. RA is an inflammatory disease, where neutrophils play important roles, and SAA is thought to participate in the inflammatory reaction by being a neutrophil chemoattractant and inducer of proinflammatory cytokines. The biological effects of SAA are reportedly mediated mainly through formyl peptide receptor like-1 (FPRL1), a G protein-coupled receptor (GPCR) belonging to the formyl peptide receptor family. Here, we confirmed the affinity of SAA for FPRL1 by showing that stably transfected HL-60 cells expressing FPRL1 were activated by SAA and that the response was inhibited by the use of the FPRL1-specific antagonist WRWWWW (WRW4). We also show that SAA activates the neutrophil NADPH-oxidase and that a reserve pool of receptors is present in storage organelles mobilized by priming agents such as TNF-alpha and LPS from Gram-negative bacteria. The induced activity was inhibited by pertussis toxin, indicating the involvement of a GPCR. However, based on FPRL1-specific desensitization and use of FPRL1 antagonist WRW4, we found the SAA-mediated effects in neutrophils to be independent of FPRL1. Based on these findings, we conclude that SAA signaling in neutrophils is mediated through a GPCR, distinct from FPRL1. Future identification and characterization of the SAA receptor could lead to development of novel, therapeutic targets for treatment of RA.
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