scholarly journals Transcriptional Profiling of Mouse Eosinophils Identifies Distinct Gene Signatures Following Cellular Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Avishay Dolitzky ◽  
Guy Shapira ◽  
Sharon Grisaru-Tal ◽  
Inbal Hazut ◽  
Shmulik Avlas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Inflammatory Responses ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Bioinformatics Analyses ◽  
E Coli ◽  
Ifn Γ ◽  
Transcriptome Signature

Eosinophils are multifunctional, evolutionary conserved leukocytes that are involved in a plethora of responses ranging from regulation of tissue homeostasis to host defense and cancer. Eosinophils have been studied mostly in the context of Type 2 inflammatory responses such as those found in allergy. Nonetheless, it is now evident that they participate in Type 1 inflammatory responses and can respond to Type 1 cytokines such as IFN-γ. Recent data suggest that the pleotropic roles of eosinophils are due to heterogeneous responses to environmental cues. Despite this, the activation profile of eosinophils, in response to various stimuli is yet to be defined. To better understand the transcriptional spectrum of eosinophil activation, we exposed eosinophils to Type 1 (e.g. IFN-γ, E. coli) vs. Type 2 (e.g. IL-4) conditions and subjected them to global RNA sequencing. Our analyses show that IL-4, IFN-γ, E. coli and IFN-γ in the presence of E. coli (IFN-γ/E. coli)-stimulated eosinophils acquire distinct transcriptional profiles, which polarize them towards what we termed Type 1 and Type 2 eosinophils. Bioinformatics analyses using Gene Ontology based on biological processes revealed that different stimuli induced distinct pathways in eosinophils. These pathways were confirmed using functional assays by assessing cytokine/chemokine release (i.e. CXCL9, CCL24, TNF-α and IL-6) from eosinophils following activation. In addition, analysis of cell surface markers highlighted CD101 and CD274 as potential cell surface markers that distinguish between Type 1 and Type 2 eosinophils, respectively. Finally, the transcriptome signature of Type 1 eosinophils resembled that of eosinophils that were obtained from mice with experimental colitis whereas the transcriptome signature of Type 2 eosinophils resembled that of eosinophils from experimental asthma. Our data demonstrate that eosinophils are polarized to distinct “Type 1” and “Type 2” phenotypes following distinct stimulations. These findings provide fundamental knowledge regarding the heterogeneity of eosinophils and support the presence of transcriptional differences between Type 1 and Type 2 cells that are likely reflected by their pleotropic activities in diverse disease settings.

Responses of inbred mouse strains to infection with intestinal nematodes

2003 ◽  
Vol 77 (2) ◽  
pp. 119-124 ◽  
Author(s):  
M.S. Dehlawi ◽  
P.K. Goyal
Keyword(s):  
Time Course ◽  
Inflammatory Responses ◽  
Trichinella Spiralis ◽  
Inbred Mice ◽  
Paneth Cell ◽  
High Responder ◽  
Mouse Strains ◽  
Ifn Γ

AbstractComparisons were made of the immune and inflammatory responses of four strains of inbred mice to infection with the intestinal nematodes Trichinella spiralis and Nippostrongylus brasiliensis to determine whether genetically determined ‘high responsiveness’ to infection, seen most clearly in intestinal responses, is independent of the parasite concerned and necessarily correlated with protection. The time course of infection was followed by counting adult worms at intervals after infection. Mucosal mast cells and Paneth cell numbers were determined as indices of the intestinal inflammatory response. Levels of IgG2a and IgG1 antibodies and of the cytokines IFN-γ and IL-5 released from in vitro-stimulated mesenteric node lymphocytes were measured to assess type 1 and type 2 responses. NIH and CBA mice were the most resistant to T. spiralis and N. brasiliensis respectively, resistance in each case being correlated with the most intense intestinal inflammatory responses. C57BL/10 (B10) and B10.BR were the least resistant to T. spiralis, but were as resistant as CBA to N. brasiliensis, despite their intestinal inflammatory responses to both parasites being much lower than the other two strains. Mice infected with T. spiralis made the expected switch from a type 1 (IFN-γ) to a type 2 (IL-5) response between days 2 and 8, and there were no significant differences in levels of these cytokines between the strains. In contrast, when infected with N. brasiliensis, CBA showed an IFN-γ response at day 4, all strains switching to IL-5 by day 8 and NIH mice releasing the greatest amount of IL-5. The results indicate that the ‘high responder’ phenotype to intestinal nematode infection is in part determined by host characteristics, but is also determined by the parasite concerned – seen most clearly by the differences between NIH and CBA when infected with T. spiralis and N. brasiliensis. The fact that ‘low responder’ B10 background mice were more resistant to N. brasiliensis than ‘high responder’ NIH implies that each parasite elicits a particular pattern of protective host responses, rather than parasites being differentially susceptible to the same response profile.

scholarly journals Bifidobacterial Species Differentially Affect Expression of Cell Surface Markers and Cytokines of Dendritic Cells Harvested from Cord Blood

2004 ◽  
Vol 11 (4) ◽  
pp. 686-690 ◽  
Author(s):  
Sarah L. Young ◽  
Mary A. Simon ◽  
Margaret A. Baird ◽  
Gerald W. Tannock ◽  
Rodrigo Bibiloni ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Cell Surface ◽  
Cord Blood ◽  
Cell Activation ◽  
Bifidobacterium Longum ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Atopic Diseases ◽  
Dendritic Cell Activation

ABSTRACT The gut microbiota may be important in the postnatal development of the immune system and hence may influence the prevalence of atopic diseases. Bifidobacteria are the most numerous bacteria in the guts of infants, and the presence or absence of certain species could be important in determining the geographic incidence of atopic diseases. We compared the fecal populations of bifidobacteria from children aged 25 to 35 days in Ghana (which has a low prevalence of atopy), New Zealand, and the United Kingdom (high-prevalence countries). Natal origin influenced the detection of bifidobacterial species in that fecal samples from Ghana almost all contained Bifidobacterium infantis whereas those of the other children did not. Choosing species on the basis of our bacteriological results, we tested bifidobacterial preparations for their effects on cell surface markers and cytokine production by dendritic cells harvested from cord blood. Species-specific effects on the expression of the dendritic-cell activation marker CD83 and the production of interleukin-10 (IL-10) were observed. Whereas CD83 expression was increased and IL-10 production was induced by Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum, B. infantis failed to produce these effects. We concluded that B. infantis does not trigger the activation of dendritic cells to the degree necessary to initiate an immune response but that B. bifidum, B. longum, and B. pseudocatenulatum induce a Th2-driven immune response. A hypothesis is presented to link our observations to the prevalence of atopic diseases in different countries.

Neonatal stem cells exhibit specific characteristics in function, proliferation, and cellular signaling that distinguish them from their adult counterparts

2008 ◽  
Vol 294 (5) ◽  
pp. R1491-R1497 ◽  
Author(s):  
Troy A. Markel ◽  
Meijing Wang ◽  
Paul R. Crisostomo ◽  
Maiuxi C. Manukyan ◽  
Jeffrey A. Poynter ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Surface ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Local Inflammatory Response ◽  
Cell Counts ◽  
Marrow Mesenchymal Stem Cells ◽  
Growth Factor Production ◽  
Erk Inhibition ◽  
Different Levels

Stem cells may be a novel treatment modality for organ ischemia, possibly through beneficial paracrine mechanisms. Stem cells from older hosts have been shown to exhibit decreased function during stress. We therefore hypothesized that 1) neonatal bone marrow mesenchymal stem cells (nBMSCs) would produce different levels of IL-6, VEGF, and IGF-1 compared with adults (aBMSCs) when stimulated with TNF or LPS; 2) differences in cytokines would be due to distinct cellular characteristics, such as proliferation or pluripotent potential; and 3) differences in cytokines would be associated with differences in p38 MAPK and ERK signaling within nBMSCs. BMSCs were isolated from adult and neonatal mice. Cells were exposed to TNF or LPS with or without p38 or ERK inhibition. Growth factors were measured via ELISA, proliferation via daily cell counts, cell surface markers via flow cytometry, and pluripotent potential via alkaline phosphatase activity. nBMSCs produced lower levels of IL-6 and VEGF, but higher levels of IGF-1 under basal conditions, as well as after stimulation with TNF, but not LPS. Neonatal and adult BMSCs had similar pluripotent potentials and cell surface markers, but nBMSCs proliferated faster. Furthermore, p38 and ERK appeared to play a more substantial role in nBMSC cytokine and growth factor production. Neonatal stem cells may aid in decreasing the local inflammatory response during ischemia, and could possibly be expanded more rapidly than adult cells prior to therapeutic use.

Sign in / Sign up

Export Citation Format

Share Document