Temperature triggers immune evasion by Neisseria meningitidis.
Neisseria meningitidis has several strategies to evade complement-mediated killing, and these contribute to its ability to cause septicaemic disease and meningitis. However, the meningococcus is primarily an obligate commensal of the human nasopharynx, and it is unclear why the bacterium has evolved exquisite mechanisms to avoid host immunity. Here we demonstrate that mechanisms of meningococcal immune evasion and resistance against complement increase in response to an increase in ambient temperature. We have identified three independent RNA thermosensors located in the 5' untranslated regions of genes necessary for capsule biosynthesis, the expression of factor H binding protein, and sialylation of lipopolysaccharide, which are essential for meningococcal resistance against immune killing. Therefore increased temperature (which occurs during inflammation) acts as a 'danger signal' for the meningococcus, enhancing its defence against human immune killing. Infection with viral pathogens, such as influenza, leads to inflammation in the nasopharynx with an increased temperature and recruitment of immune effectors. Thermoregulation of immune defence could offer an adaptive advantage to the meningococcus during co-infection with other pathogens, and promote the emergence of virulence in an otherwise commensal bacterium.
Sir William Dunn School of Pathology, University of Oxford, Sir Parks Road, Oxford OX1 3RE, UK.
Edmund
E
Loh
Elisabeth
E
Kugelberg
Alexander
A
Tracy
Qian
Q
Zhang
Bridget
B
Gollan
Helen
H
Ewles
Ronald
R
Chalmers
Vladimir
V
Pelicic
Christoph M
CM
Tang
D020121:5' Untranslated Regions / Q000235:genetics; D016667:Bacterial Capsules / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D057131:Immune Evasion / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008589:Meningococcal Infections / Q000276:immunology* / Q000382:microbiology; D009345:Neisseria meningitidis / Q000235:genetics / Q000502:physiology*; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D013696:Temperature; D013697:Thermosensing / Q000235:genetics
D020121:5' Untranslated Regions; D001426:Bacterial Proteins; D008070:Lipopolysaccharides; D012329:RNA, Bacterial