MyD88-dependent influx of monocytes and neutrophils impairs lymph node B cell responses to chikungunya virus infection via Irf5, Nos2 and Nox2.
Mary K McCarthyGlennys V ReynosoEmma S WinklerMatthias MackMichael S DiamondHeather D HickmanThomas E MorrisonPublished in: PLoS pathogens (2020)
Humoral immune responses initiate in the lymph node draining the site of viral infection (dLN). Some viruses subvert LN B cell activation; however, our knowledge of viral hindrance of B cell responses of important human pathogens is lacking. Here, we define mechanisms whereby chikungunya virus (CHIKV), a mosquito-transmitted RNA virus that causes outbreaks of acute and chronic arthritis in humans, hinders dLN antiviral B cell responses. Infection of WT mice with pathogenic, but not acutely cleared CHIKV, induced MyD88-dependent recruitment of monocytes and neutrophils to the dLN. Blocking this influx improved lymphocyte accumulation, dLN organization, and CHIKV-specific B cell responses. Both inducible nitric oxide synthase (iNOS) and the phagocyte NADPH oxidase (Nox2) contributed to impaired dLN organization and function. Infiltrating monocytes expressed iNOS through a local IRF5- and IFNAR1-dependent pathway that was partially TLR7-dependent. Together, our data suggest that pathogenic CHIKV triggers the influx and activation of monocytes and neutrophils in the dLN that impairs virus-specific B cell responses.
Keyphrases
- nitric oxide synthase
- lymph node
- immune response
- dendritic cells
- toll like receptor
- peripheral blood
- nitric oxide
- aedes aegypti
- zika virus
- healthcare
- dengue virus
- liver failure
- neoadjuvant chemotherapy
- type diabetes
- machine learning
- inflammatory response
- adipose tissue
- metabolic syndrome
- sars cov
- hepatitis b virus
- diabetic rats
- oxidative stress
- insulin resistance
- reactive oxygen species
- artificial intelligence
- nuclear factor
- rectal cancer
- mechanical ventilation
- nucleic acid