The immunomodulatory effect of antimicrobial peptide HPA3P restricts Brucella abortus 544 infection in BALB/c mice
Abstract The discovery of antimicrobial peptides (AMPs) in recent years has been promising for the treatment of multidrug resistant pathogenic microbes. Brucellosis is still considered one of the most common zoonoses in the world. In this study, we evaluated the effect HPA3P peptide in the bacterial uptake and intracellular growth of Brucella abortus ( B. abortus) 544 in murine macrophages RAW 264.7. HPA3P was further utilized in a mouse model for infection and treatment. This peptide did not show cytotoxicity or bactericidal effect to B. abortus . However, it inhibited bacterial internalization at 0, 15 and 30 min incubation at two different doses at 12 and 24 μM as well as reduced intracellular growth after 2, 24 and 48 h incubation. Mice treated with HPA3P demonstrated a significant 1.01-log reduction ( P 0.0001) and spleen weight reduction compared to the nanocarrier control ( P 0.01). Significant increases in key cytokines Interferon-γ (IFN-γ) and Tumor necrosis factor (TNF) at 3, 7 and 14 days post-infection were observed in HPA3P treated mice similar to the antibiotic control group with both compared to the nanocarrier control. Monocyte chemoattractant protein-1 (MCP-1) was also heightened at 14 days post-infection. Histopathological analysis also suggests reduced bacterial granuloma in the liver and spleens of HPA3P treated group compared with the nanocarrier control group. In this study, the modulation of crucial cytokines IFN-γ and TNF might have led to a considerable reduction in the proliferation of B. abortus in a mouse model of brucellosis. Further investigation might be required to maximize the efficacy of HPA3P treatment in murine brucellosis. Highlights HPA3P did not cause any cytotoxicity or bactericidal effect to B. abortus . HPA3P inhibited bacterial internalization and reduced intracellular growth within macrophages. Mice treated with HPA3P demonstrated a significant log reduction and spleen weight reduction compared to the nanocarrier control. Significant increases in key cytokines IFN-γ and TNF were observed in HPA3P treated mice. Histopathological analysis suggests reduced bacterial granuloma in the liver and spleens of HPA3P treated group compared to nanocarrier group.
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