Wednesday, February 25, 2015

Inflammatory signals from the peripheral tissue modulates immune response in lymph nodes

Very unusual results have been published in journal Science. This study came from Facundo Batista's lab at the London Research Institute.

The authors studied lymph node's adaptive re-organization in response to peripheral inflammatory signals, with the focus on CD169-positive macrophages. These specialized macrophages are ordinarily positioning themselves in the subcapsular sinus of the lymph nodes intercepting any incoming antigens from the peripheral tissue for presentation to B cells.

Using different type of inflammatory signals (live or dead bacteria, live or inactivated viruses, or TLR agonists), the authors observed that live bacteria or virus or TLR agonist injected in the mouse footpads caused temporal disruption of CD169+ macrophage layer in the draining lymph node.   

Further experiments showed that disruption of CD169+ macrophage layer in the draining lymph node upon CpG injection was abolished in mice selectively deficient for MyD88 signaling in dendritic cells.

In addition the authors noticed that disruption of CD169+ macrophage layer was also reduced in CCR7-KO mice where DCs could not migrate from the peripheral tissue to the lymph node.  

To understand physiological consequences of CD169+ macrophage layer disruption, the authors injected labeled B cell antigen into footpad following initial CpG or PBS (control) injection (+ 4 / +7 days later). These experiments revealed that fewer CD169+ macrophage and fewer antigen-specific B cells could acquire antigen following CpG injection.   

More importantly, the authors showed that initial CpG injection reduced subsequent anti-viral antibody response.

In summary, these results shows that initial inflammatory signals coming from peripheral tissue disrupt CD169+ macrophage layer and antibody response to subsequently injected antigen. 

This is strange results. No good explanation is given. For one, the authors did not provide results regarding viral titre or tissue pathology in mice injected with primary CpG. 2nd, isn't lymph nodes function to respond to the inflammation in peripheral tissue? How could it be beneficial for the host to shut down immune response following inflammatory stimuli? Could it be that lymph nodes are modified to activate different type of immune response (CTL?)

David Usharauli

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