Macrophages (MF) are known to exhibit distinct responses to viral and bacterial infection,
but how they react when exposed to the pathogens in succession is less well understood.
Accordingly, we determined the effect of a rubella virus (RV)-induced infection followed by
an LPS-induced challenge on cytokine production, signal transduction and metabolic
pathways in human GM (M1-like)- and M (M2-like)-MF. We found that infection of both
subsets with RV resulted in a low TNF-a and a high interferon (IFN, type I and type III)
release whereby M-MF produced far more IFNs than GM-MF. Thus, TNF-a production in
contrast to IFN production is not a dominant feature of RV infection in these cells. Upon
addition of LPS to RV-infected MF compared to the addition of LPS to the uninfected cells
the TNF-a response only slightly increased, whereas the IFN-response of both subtypes
was greatly enhanced. The subset specific cytokine expression pattern remained
unchanged under these assay conditions. The priming effect of RV was also observed
when replacing RV by IFN-b one putative priming stimulus induced by RV. Small amounts
of IFN-b were sufficient for phosphorylation of Stat1 and to induce IFN-production in
response to LPS. Analysis of signal transduction pathways activated by successive
exposure of MF to RV and LPS revealed an increased phosphorylation of NFkB (MMF),
but different to uninfected MF a reduced phosphorylation of ERK1/2 (both
subtypes). Furthermore, metabolic pathways were affected; the LPS-induced increase
in glycolysis was dampened in both subtypes after RV infection. In conclusion, we show
that RV infection and exogenously added IFN-b can prime MF to produce high amounts
of IFNs in response to LPS and that changes in glycolysis and signal transduction are
associated with the priming effect. These findings will help to understand to what extent
MF defense to viral infection is modulated by a following exposure to a bacterial infection.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84309 |
| Date | 24 March 2023 |
| Creators | Schilling, Erik, Grahnert, Anja, Pfeiffer, Lukas, Koehl, Ulrike, Claus, Claudia, Hauschildt, Sunna |
| Publisher | Frontiers Research Foundation |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1664-3224, 772595 |
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