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Table 1.

Primary antibodies used in study.

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Table 2.

Secondary antibodies used in studya.

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Fig 1.

Schematic outlining relationships and properties of polarized macrophages.

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Fig 2.

Mean number (Log μm2) of macrophages (AM-3K) classified as host defense (IFN-γ, IL-1β, IL-12, IL-23, uNOS, TNF-α, and TLR4) or regulation of inflammation (IL-1Ra, IL-10m CD163, CD206, and TGF-β), present in frozen bovine mid-ileal tissue sections collected from cows naturally infected with Mycobacterium avium subsp. paratuberculosis (subclinical and clinical), compared to uninfected control cows.

Asterisks denote statistical significance: * p<0.05; ** p<0.01; *** p<0.001; **** p<0.0001.

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Fig 3.

Representative IF labeling in frozen bovine mid-ileal tissue, comparing cows subclinically and clinically infected with Mycobacterium avium subsp. paratuberculosis (MAP).

Nuclear staining was performed using 4’,6- diamidino-2-phenylindole, dihydrochloride (DAPI, blue). Each merged image was selected as an example of representative IF labeling from a single cow. (A and E) CD163; (B and F) TLR4; (C and G) AM-3K; (D and H) merged image of CD163, TLR4 and AM-3K; (I and M) CD206; (J and N) uNOS; (K and O) AM-3K; (L and P) merged image of CD206, uNOS and AM-3K.

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Fig 4.

Mean number (Log μm2) of total macrophages (AM-3K) classified as either host defense or regulation of inflammation macrophages.

IF staining was performed on frozen bovine mid-ileal tissue sections collected from cows naturally infected with Mycobacterium avium subsp. paratuberculosis (subclinical and clinical), compared to uninfected control cows. Asterisks denote statistical significance: ** p<0.01.

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Fig 5.

Pairwise Pearson correlations for total number of macrophages (Mφ) with host defense Mφ phenotypes.

(A) correlation between total Mφ and number of IFN-γ+ Mφ for control cows; (B) correlation between total Mφ and number of IL-12+ Mφ for control cows (○ and solid line) and subclinical cows (● and dotted line); (C) correlation between total Mφ and number of IL-1β+ Mφ for subclinical cows; and (D) correlation between total Mφ and number of IL-23+ Mφ for subclinical cows).

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Table 3.

Pairwise Pearson correlations between cytokines colocalized within host defense macrophages.

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Fig 6.

Pairwise Pearson correlations for total number of macrophages (Mφ) with resolution and repair Mφ phenotypes.

(A) correlation between total Mφ and number of IL-1Ra+ Mφ for subclinical cows; (B) correlation between total Mφ and number of IL-10+ Mφ for subclinical cows (● and dotted line) and clinical cows (□ and dotted line); (C) correlation between total Mφ and number of TGF-β+ Mφ for subclinical cows; and (D) correlation between total Mφ and number of CD206+ Mφ for subclinical cows.

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Table 4.

Pair-wise Pearson correlations between cytokines colocalized within resolution and repair macrophage phenotypes.

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Table 4 Expand