Abstract
Natural killer (NK) cells are one of the types of innate immune cells to remove pathogen-infected cells and modulate inflammatory immune responses. Recent studies have revealed that NK cells could enhance vaccine efficacy by coordinating the innate and adaptive immune responses. In this study, we have evaluated the efficacy of intranasal ovalbumin (OVA) immunization with a monophosphoryl lipid A (MPL) and polyriboinosinic polyribocytidylic acid (poly I:C) combination adjuvant in promoting NK cell recruitment, differentiation, and activation. The frequencies of NK cells were positively correlated with those of dendritic cells (DCs) at the site of immunization. Moreover, the activated NK cells and DCs by the MPL + poly I:C combination adjuvant induced activations of each other cells in vitro. Taken together, this study suggested that the MPL and poly I:C combination adjuvant in OVA vaccination mediated NK cell activation and cellular crosstalk between NK cells and DCs, suggesting a promising vaccine adjuvant candidate for promoting cellular immune responses.
Highlights
The innate immune system serves as the first line of defense against non-self-antigens invading the body in mammals [1]
Natural killer (NK) cells are described as the major effector cells toward cancer in innate immunity with a capacity to kill abnormal cells based on levels of major histocompatibility complex-I (MHC-I) expressing on those cells, and whose abilities resemble CD8 T cell functions in adaptive immunity [3,4,5]
We investigated the NK cell responses stimulated by monophosphoryl lipid A (MPL), polyribocytidylic acid (poly I):C, and combined MPL and poly I:C adjuvants with ovalbumin (OVA) immunization in murine models to validate the cellular mechanisms of the combination adjuvant
Summary
The innate immune system serves as the first line of defense against non-self-antigens invading the body in mammals [1]. NK cells are described as the major effector cells toward cancer in innate immunity with a capacity to kill abnormal cells based on levels of major histocompatibility complex-I (MHC-I) expressing on those cells, and whose abilities resemble CD8 T cell functions in adaptive immunity [3,4,5] Besides their cytotoxic roles, activated NK cells can induce the maturation of dendritic cells (DCs), which drives the development of T helper type 1 (Th1) lymphocytes [6,7]. A combination of oligodeoxynucleotide CpG and MPL adjuvants, either in respiratory syncytial virus F protein or influenza vaccine, elicited strong antigen-specific immune responses and provided protection against either inflammatory RSV disease or influenza virus infection after a single dose vaccination, further promoting cross-protection against heterosubtypic influenza virus infection [26,27,28]. This study provided valuable information that the efficacy of MPL and poly I:C combination adjuvant in OVA vaccination might have been mediated by NK cell activation and cellular crosstalk between NK cells and DCs
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