Combinations of human lysozyme (hLYS) and antimicrobial peptides (AMPs) are known to exhibit either additive or synergistic activity, and as a result, they have therapeutic potential for persistent and antibiotic‐resistant infections. We examined hLYS activity against Pseudomonas aeruginosa when combined with six different AMPs. In contrast to prior reports, we discovered that some therapeutically relevant AMPs manifest striking antagonistic interactions with hLYS across particular concentration ranges. We further found that the synthetic AMP Tet009 can inhibit hLYS‐mediated bacterial lysis. To the best of our knowledge, these results represent the first observations of antagonism between hLYS and AMPs, and they advise that future development of lytic enzyme and AMP combination therapies considers the potential for antagonistic interactions.

Th1 responses in the liver are the basis for parenchymal damage in autoimmune hepatitis (AIH). The cellular pathways that inhibit liver Th1 responses are not well understood. BALB/c mice lacking TGF-β1 spontaneously and rapidly develop acute Th1 cell-mediated necroinflammatory hepatitis. Liver damage requires interferon gamma (IFN-γ) production by CD4+ T cells. We hypothesized that the Th1 response would also activate pathways capable of down-regulating T cell responses, specifically, a myeloid derived suppressor cell (MDSC) population. Myeloid cells were indeed abundant in liver parenchyma in histological sections of Tgfb1KO livers. Characterization of this cell type showed that they were CD11b+Gr-1+ cells that strongly suppressed T cell proliferation in vitro, thus MDSCs. By contrast, Tgfb1WT liver CD11b+Gr-1+ cells were much less abundant and exhibited no T cell suppression capabilities. Suppression required nitric oxide (NO) and cell-cell contact, but not arginase, PDL1, or H2O2. Tgfb1KO MDSCs suppressed T cell proliferation by inducing apoptosis. Further studies using Tgfb1KO/IfngKO mice showed that IFN-γ was required both for MDSC accumulation in liver as well as for MDSC suppressor activity. These results demonstrate that, during hepatitis, Th1 cells activate through IFN-γ production an MDSC negative feedback pathway that can inhibit T cell responses through NO. Why this negative feedback pathway ultimately fails in AIH remains critical to elucidate.