Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection

[Bob]

Bone-Marrow-Resident NK Cells Prime Monocytes for Regulatory Function during Infection
Michael H. Askenase et al.
Immunity
Published Online:June 09, 2015
DOI: http://dx.doi.org/10.1016/j.immuni.2015.05.011
http://www.cell.com/immunity/abstract/S1074-7613(15)00208-3

Highlights

• Monocytes acquire regulatory properties in bone marrow early during gut infection
• Infection-induced IFN-γ alters monocyte precursors in the bone marrow
• Bone-marrow-resident NK cells prime monocytes for regulatory function
• IL-12 produced in the gut activates bone marrow NK cells, instructing hematopoiesis

Summary
Tissue-infiltrating Ly6Chi monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. How and where this diversity of function is imposed remains poorly understood. Here we show that during acute gastrointestinal infection, priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Notably, natural killer (NK) cell-derived IFN-γ promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DCs) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals after tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function.

 

[Bob]

News article...

'Gut reaction' to illness found to inform immune system response
10 June 2015
http://www.medicalnewstoday.com/articles/295099.php?tw

Extract:

Prior to the study - published in Immunity - experts believed that immune cell programming only occurred once the cells had arrived at the point of injury or infection.
[...]

So far, scientists have been unable to identify how and why the monocytes are programmed as they are. To investigate, researchers led by Dr. Grainger and Dr. Yasmine Belkaid, from the National Institute of Allergy and Infectious Diseases (NIAID), examined how monocytes in mice responded to a parasitic infection.

Toxoplasmosis is caused by the parasite Toxoplasma gondii and can infect the gut through the consumption of undercooked meat. The parasite is also known to be present in the feces of cats.

The researchers discovered that as soon as the infection invaded the gut, the tissue began to communicate with other parts of the body in order to alter the immune system. Dr. Grainger explains:

"One particular cell-type in the gut, the dendritic cell, can act as a beacon sending out long-range signals to the bone marrow where monocytes are produced. Cells in the bone marrow then pick up the signal and pre-program monocytes with the appropriate function to either protect or repair."

 

[halcyon]

Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DCs) in the mucosal-associated lymphoid tissue (MALT).

I've been wondering about this lately, in the context of chronic enteroviral gut infections. It's been shown that enteroviruses directly infect peyer's patches (part of the aforementioned MALT). I have to wonder if this infection of the lymph tissue might cause some sort of dysfunction in the tissue, and if that dysfunction would cascade through the immune cells that surveil or mature in that tissue, which as this paper shows could have far reaching effects.