Dualistic immunomodulation of sub-chronic microcystin-LR exposure on the innate-immune defense system in male zebrafish

- Macrophages might be the main action site of MC-LR in the spleen.
- MC-LR has concentration-dependent dualistic influences on fish innate immune system.
- Inflammatory activation in low exposure concentration but immune inhibition at high concentration.
- Interference of environmental concentrations of MC-LR in the immune system should not be neglected.

Microcystins (MCs), produced by toxic cyanobacterial blooms that appeared world wildly in eutrophication waters, have often caused fish illness and even massive death cases. Among at least 90 structural variants, microcystin-LR (MC-LR) is the most common and toxic variant. In order to better understand innate immune responses in fish disrupted by environmental concentrations of MC-LR, male zebrafish (Danio rerio) were exposed to 0, 0.3, 1, 3, 10 and 30 μg/L MC-LR for 30 d, and the changes in splenic pathology and immunological gene expression as well as serum immune parameters were studied. In the low concentration groups (0.3, 1 and 3 μg/L), zebrafish displayed splenic inflammatory changes including the formation of melano-macrophage centers and the increase of macrophage pseudopodia, remarkable elevation of serum C3 levels, and significantly upregulated expression of innate immune-related genes (c3b, lyz, il1β, tnfα and ifnγ). In contrast, high concentrations of MC-LR (10 and 30 μg/L) resulted in the degeneration of splenic lymphocytes and macrophages, and down-regulation of immune-related genes as well as significant decreases in the level of serum C3. Furthermore, significant increases in the activity of serum ACP and ALP suggested that high concentrations of MC-LR increased permeability of macrophage plasma membrane or cellular necrosis, and subsequently decreased innate immune function. Our findings illustrated that sub-chronic exposure of MC-LR has dualistic influences on fish innate immune system with inflammatory activation at low exposure concentrations but turned to immune inhibition with the increases of exposure concentration.

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