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Background  Environmental factors are critical in the development of age-related cognitive decline and dementia. A western diet (WD) can cause nutrient deficiency and inflammation that could impact cognition directly. It is increasingly recognized that innate immune responses by brain myeloid cells, such as resident microglia, and infiltrating peripheral monocytes/macrophages may represent an essential link between a WD, cognitive decline, and dementia. Our previous data demonstrated that chronic consumption of a WD induced inflammation through brain myeloid cells in aging mice and a mouse model of Alzheimer’s disease (AD). However, the subtypes of myeloid cells that contribute to the WD-induced inflammation remain unclear.    Methods  C57BL/6J (B6), myeloid cell reporter mice (B6. Ccr2   RFP/+   Cx3cr1   GFP/+  ), and  Ccr2 -deficient mice (B6. Ccr2   RFP/RFP  ) were fed a WD or a control chow diet (CD) from 2 to 6 or 12 months of age. CD11b+CD45 lo  and CD11b+CD45 hi  cells from WD- and CD-fed B6 or  Ccr2 -deficient mice were characterized using flow cytometry, RNA-sequencing, and immunofluorescence.    Results   Ccr2 ::RFP expressing myeloid cells were significantly increased in brains of WD- compared to CD-fed mice, but were not elevated in  Ccr2 -deficient WD-fed mice. The percent of CD11b+CD45 hi  cells was significantly increased in WD- compared to CD-fed mice. Comparison of RNA-sequencing data with immune cell data in ImmGen supports that CD11b+CD45 hi  cells from WD-fed mice are enriched for peripheral monocytes and neutrophils. Ingenuity pathway analysis predicted these cells elicit proinflammatory responses that may be damaging to the brain. Using stringent criteria for gene expression levels between CD11b+CD45 hi  and CD11b+CD45 lo  cells, we identified approximately 70 genes that we predict are uniquely expressed in infiltrating cells, including  Itgal ,  Trem1 ,  and Spp1  (osteopontin, OPN ) . Finally, we show a significantly greater number of OPN+IBA1– cells in WD- compared to CD-fed mice that we propose are activated neutrophils based on ImmGen data. OPN+IBA1– cells are not significantly increased in  Ccr2 -deficient WD-fed mice.    Conclusions  These data further support the model that peripheral myeloid cells enter the brain in response to diet-induced obesity. Elucidating their contribution to age-related cognitive decline and age-related neurodegenerative diseases should offer new avenues for therapeutic intervention in Alzheimer’s disease and related dementias, where diet/obesity are major risk factors.    Electronic supplementary material  The online version of this article (10.1186/s12974-019-1527-z) contains supplementary material, which is available to authorized users.

Transcriptome profiling of brain myeloid cells revealed activation of Itgal, Trem1, and Spp1 in western diet-induced obesity