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Activates Both IL-1β and IL-1 Receptor Antagonist to Modulate Lung Inflammation during Pneumonic Plague


Inhalation of respiratory droplets containing Yersinia pestis results in a rapidly developing and lethal pneumonia. Interestingly, early interactions between Y. pestis and host cells in the lung contribute to significant immune evasion, but also ultimately result in severe innate immune activation. Our results demonstrate that Y. pestis activates pro-inflammatory cytokines IL-1β and IL-18 in the lung early during infection. However, there is very little early pulmonary inflammation while Y. pestis continues to multiply in the lung compartment. We show that the host protein IL-1RA is activated concurrently with IL-1β, attenuating early immune activation by this cytokine. We propose that this allows the organism to replicate to high titers, eventually triggering a vigorous inflammatory response and facilitating aerosol transmission. Therefore, evaluating early host activation of IL-1RA by Y. pestis may provide therapeutic targets against pneumonic plague.


Vyšlo v časopise: Activates Both IL-1β and IL-1 Receptor Antagonist to Modulate Lung Inflammation during Pneumonic Plague. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004688
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004688

Souhrn

Inhalation of respiratory droplets containing Yersinia pestis results in a rapidly developing and lethal pneumonia. Interestingly, early interactions between Y. pestis and host cells in the lung contribute to significant immune evasion, but also ultimately result in severe innate immune activation. Our results demonstrate that Y. pestis activates pro-inflammatory cytokines IL-1β and IL-18 in the lung early during infection. However, there is very little early pulmonary inflammation while Y. pestis continues to multiply in the lung compartment. We show that the host protein IL-1RA is activated concurrently with IL-1β, attenuating early immune activation by this cytokine. We propose that this allows the organism to replicate to high titers, eventually triggering a vigorous inflammatory response and facilitating aerosol transmission. Therefore, evaluating early host activation of IL-1RA by Y. pestis may provide therapeutic targets against pneumonic plague.


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Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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