Trying to understand how viruses (my thing) trigger asthma exacerbations (a clinical thing) via activation of multiple inflammatory pathways (an immunology thing designed to be impossible to follow unless you love keeping tract of tiny little initialisms and what each of them do, did and used to be called 5-minutes ago) is heavy going. This Letter somehow adds to the field without all of "that".
The authors obtained mononuclear cells from the lower respiratory tract of 10 volunteers with mild atopic (allergic) asthma, by bronchoalveolar lavage. That was Day zero (D0). At 48-hours (D2) the donors were given an allergen and cells were collected by BAL again.
Macrophages were obtained from the D0 and D2 cells (they stick to the plastic culture flasks, other blood cells don't) and they were then challenged with 1 of 3 rhinoviruses (RV); either RV-A16, RV-B14 or RV-A2. I say challenged because rhinovirus doesn't replicate within macrophages (also written in shorthand as MΦ) but they do interact with them.
The team then looked at a bunch of initialisms which represent some potent chemicals called chemokines:
- CXCL10 (IP-10)
- C-X-C motif chemokine 10; formerly interferon gamma-induced protein 10
- secreted by macrophages that have been activated by RV interaction
- also secreted by endothelial cells and fibroblasts
- secreted from cells in response to interferon gamma (IFN-γ)
- signal the recruitment of immune cells (monocytes/macrophages, T cells, natural killer [NK] cells and dendritic cells) that take charge of getting rid of virus
- C-X-C motif chemokine 11; formerly known as Interferon-inducible T-cell alpha chemoattractant (I-TAC) and Interferon-gamma-inducible protein 9 (IP-9)
- also secreted by macrophages that have been activated by RV interaction
- secreted in the pancreas and liver
- secreted from cells in response to IFN-γ and IFN-β
- interacts with cell surface receptor, CXCR3
- recruits activated T-cells
- Chemokine ligand 2; formerly known as monocyte chemotactic protein-1 (MCP-1) or small inducible cytokine A2
- can also be secreted by macrophages after RV exposure
- also secreted by monocytes and dendritic cells and expressed by neurons, astrocytes and microglia
- recruits monocytes and basophils
- binds to the cell surface receptors CCR2 and CCR4
- Chemokine ligand 2; formerly known as monocyte chemoattractant protein-2 (MCP-2)
- can be secreted by macrophages after RV exposure
- recruits mast cells, eosinophils, basophils, monocytes, T-cells and NK cells
- binds to cell surface receptors CCR1, CCR2B and CCR5
- D2 samples that were not challenged with virus made less CXCL10, more CCL2 and nothing much changed in levels of CXCL11 or CCL8.
- D0 samples incubated with RV saw a statistically significant rise in the amount of all 4 chemokines
- D2 samples incubated with RV saw a rise in CCL2 but a drop in CXCL10 and CXCL11 but no effect on CCL8
So the first batch of findings indicate that RV infection does not induce the same chemokine response from lower airway macrophages of people with allergy that have just been exposed to an allergen (think pollen or dust mite).
Further, it identified that in macrophages, a key immune cell in controlling viral infections in the airways, may not respond as effectively to RV infection in the body if such infection follows an allergen hit. At the same time, increasing CCL2 may increase inflammation by attracting those types of cells (eosinophils, neutrophils and more macrophages).
The team also went on to look at the levels of the 2 known RV cellular receptors, intercellular adhesion molecule I (ICAM-1) and the low density lipoprotein receptor (LDLR) and LDLR-related protein-1 (LRP-1). Receptors have been used as a way to categorise RVs in the past and some adhere to this when making choices in the design of their immunology research relating to RVs.
- D2 macrophgaes had raised levels of ICAM-1 on the cellular surface but lowered levels of LDLR and LRP-1
- Other blood cells showed no difference in receptor levels
- Allergen-induced effects on RV receptor expression are distinct from its effects on chemokine levels
Great to know that RVs are ubiquitous and so are allergens!
- Information on some cytokines and cell signalling following viral infection
- Wikipedia as a starter for detail on cytokines