Ag-presenting dendritic cells present viral Ags to T cells after uptake of apoptotic bodies derived from virus-infected cells in vitro. However, it is unclear whether apoptotic virus-infected cells are capable of generating immunity in vivo. In this study, we show that inoculation of mice with apoptotic HIV-1/murine leukemia virus (MuLV)-infected cells induces HIV-1-specific immunity. Immunization with apoptotic HIV-1/MuLV-infected syngeneic splenocytes resulted in strong Nef-specific CD8+ T cell proliferation and p24-induced CD4+ and CD8+ T cell proliferation as well as IFN-γ production. In addition, systemic IgG and IgA as well as mucosa-associated IgA responses were generated. Moreover, mice vaccinated with apoptotic HIV-1/MuLV cells were protected against challenge with live HIV-1/MuLV-infected cells, whereas mice vaccinated with apoptotic noninfected or MuLV-infected splenocytes remained susceptible to HIV-1/MuLV. These data show that i.p. immunization with apoptotic HIV-1-infected cells induces high levels of HIV-1-specific systemic immunity, primes for mucosal immunity, and induces protection against challenge with live HIV-1-infected cells in mice. These findings may have implications for the development of therapeutic and prophylactic HIV-1 vaccines.

Secondary infections with Streptococcus pneumoniae (SP) are frequently observed following influenza A virus (IAV) infection and have a substantial impact on global health. Despite this, the basis for the disease progression is incompletely understood. To investigate the effect of co-infection on human monocyte-derived dendritic cells (MDDCs) we analysed the expression of clinically important pro-inflammatory and immune-modulatory cytokines. IAV infection or treatment with supernatants from IAV-infected cell cultures resulted in priming of the DCs which subsequently influenced the production of IL-12p70, as well as IL-6, following SP infection. Co-infection of the same cell was not required but this effect was dependent on the time, dose and duration of the infections, as well as pathogen viability, bacterial uptake and endosome acidification. Bacterially infected cells were characterized as the main producers of IL-12p70. Finally, we showed that type I interferons were primarily responsible for the priming of IL-12p70 that was observed by infection with IAV. These results provide a probable mechanism for the elevated levels of particular cytokines observed in IAV and SP co-infected cell cultures with implications for the pathogenic outcome observed during in vivo infection.

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Macrophages surround the sebaceous glands both in the healthy and the inflamed pilosebaceous unit; however, the reason for this phenomenon and the possible role of sebocytes in it has not yet been investigated. By performing immunohistochemistry on healthy biopsies, we could demonstrate that macrophages in the close proximity of sebaceous glands are exclusively alternatively activated (CD163 + /FXIII-A + /CD206 + /CD209 +). To investigate if sebocytes contribute to the differentiation, polarization and function of macrophages, human peripheral blood monocytes were differentiated and activated in the presence of either supernatant from the human SZ95 sebocyte cell line, or major sebum lipid components such as oleic-, linoleic-, palmitic-, stearic-acids and squalene. Our results showed that with the secretion of CXCL8, sebocytes could exert a chemoattractant effect towards monocytes, while sebocytes derived lipids promoted monocyte differentiation into alternatively activated macrophages as marked by the up-regulation of CD206, CD209 and FXIII-A. Moreover, detection of the produced IL-1b, IL-6 and TNFa protein levels by Propionibacterium acnes activated macrophages revealed a selective inflammatory effect for the various sebum lipids. Our results altogether suggest a role for sebaceous glands in initiating and modulating innate immune responses via their proteins and lipids that are of possible pathologic and therapeutic relevance.