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Neutrophil Recruitment to Lymph Nodes Limits Local Humoral Response to


Highly antibiotic resistant Staphylococcus aureus (S. aureus) are an important human pathogen and major cause of hospital acquired infections. An early host defense mechanism against bacterial infection is neutrophil recruitment, which helps eliminate the bacteria at the site of invasion. However, unless quickly neutralized, pathogens such as S. aureus can gain access to nearby lymph nodes via draining lymphatics. Lymph nodes protect the host by mobilizing additional resources that limit further pathogen dissemination. These include recruitment of neutrophils to the lymph node to directly target pathogens and the initiation of adaptive immune mechanisms, such as the humoral immune response, which transforms B lymphocytes capable of making pathogen specific antibodies into antibody producing plasma cells. Using a mouse model that allows direct visualization of lymphocytes, neutrophils, and fluorescently-labeled S. aureus in lymph nodes, we document the rapid appearance of bacteria in the lymph node following local S. aureus infection. We characterize the dynamic influx of neutrophils that occurs as a consequence and reveal direct B cell-neutrophil interactions within the lymph node parenchyma. We find that while lymph node neutrophils rapidly engage bacteria, they limit the subsequent humoral immune response likely by producing Transforming Growth Factor-β1, a factor known to limit B cell responses. These finding have important implication for our understanding of B cell responses against potent pathogens such as S. aureus and for the design of effective vaccines.


Vyšlo v časopise: Neutrophil Recruitment to Lymph Nodes Limits Local Humoral Response to. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004827
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004827

Souhrn

Highly antibiotic resistant Staphylococcus aureus (S. aureus) are an important human pathogen and major cause of hospital acquired infections. An early host defense mechanism against bacterial infection is neutrophil recruitment, which helps eliminate the bacteria at the site of invasion. However, unless quickly neutralized, pathogens such as S. aureus can gain access to nearby lymph nodes via draining lymphatics. Lymph nodes protect the host by mobilizing additional resources that limit further pathogen dissemination. These include recruitment of neutrophils to the lymph node to directly target pathogens and the initiation of adaptive immune mechanisms, such as the humoral immune response, which transforms B lymphocytes capable of making pathogen specific antibodies into antibody producing plasma cells. Using a mouse model that allows direct visualization of lymphocytes, neutrophils, and fluorescently-labeled S. aureus in lymph nodes, we document the rapid appearance of bacteria in the lymph node following local S. aureus infection. We characterize the dynamic influx of neutrophils that occurs as a consequence and reveal direct B cell-neutrophil interactions within the lymph node parenchyma. We find that while lymph node neutrophils rapidly engage bacteria, they limit the subsequent humoral immune response likely by producing Transforming Growth Factor-β1, a factor known to limit B cell responses. These finding have important implication for our understanding of B cell responses against potent pathogens such as S. aureus and for the design of effective vaccines.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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