The early monocytic response to cytomegalovirus infection is MyD88 dependent but occurs independently of common inflammatory cytokine signals

Wikstrom, Matthew E., Khong, Andrea, Fleming, Peter, Kuns, Rachel, Hertzog, Paul J., Frazer, Ian H., Andoniou, Christopher E., Hill, Geoffrey R. and Degli-Esposti, Mariapia A. (2014) The early monocytic response to cytomegalovirus infection is MyD88 dependent but occurs independently of common inflammatory cytokine signals. European Journal of Immunology, 44 2: 409-419. doi:10.1002/eji.201243109


Author Wikstrom, Matthew E.
Khong, Andrea
Fleming, Peter
Kuns, Rachel
Hertzog, Paul J.
Frazer, Ian H.
Andoniou, Christopher E.
Hill, Geoffrey R.
Degli-Esposti, Mariapia A.
Title The early monocytic response to cytomegalovirus infection is MyD88 dependent but occurs independently of common inflammatory cytokine signals
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
1521-4141
Publication date 2014
Year available 2013
Sub-type Article (original research)
DOI 10.1002/eji.201243109
Volume 44
Issue 2
Start page 409
End page 419
Total pages 11
Place of publication Weinheim, Germany
Publisher Wiley - V C H Verlag
Collection year 2014
Language eng
Abstract Cytomegalovirus latently infects myeloid cells; however, the acute effects of the virus on this cell subset are poorly characterised. We demonstrate that systemic cytomegalovirus infection induced rapid activation of monocytes in the bone marrow, characterised by upregulation of CD69, CD11c, Ly6C and M-CSF receptor. Activated bone marrow monocytes were more sensitive to M-CSF and less sensitive to granulocyte-monocyte colony stimulating factor in vitro, resulting in the generation of more macrophages and fewer dendritic cells, respectively. Monocyte activation was also observed in the periphery and resulted in significant accumulation of monocytes in the spleen. MyD88 expression was required within the haematopoietic compartment to initiate monocyte activation and recruitment. However, monocytes lacking MyD88 were activated and recruited in the presence of MyD88-sufficient cells in mixed bone marrow chimeras, indicating that once initiated, the process was MyD88 independent. Interestingly, we found that monocyte activation occurred in the absence of the common inflammatory cytokines, namely type I interferons (IFNs), IL-6, TNF-α and IL-1 as well as the NLRP3 inflammasome adaptor protein, ASC. We also excluded a role for the chemokine-like protein MCK-2 (m131/129) expressed by murine CMV. Taken together, these results challenge the notion that a single inflammatory cytokine mediates activation and recruitment of monocytes in response to infection.
Keyword Bone marrow
Cytokines
Infectious diseases
Innate immunity
Monocytes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 16 December 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
 
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