Probiotic effects on innate cell defences

A large body of work concerned with definition of probiotic effects on the immune system has focused on innate cell responses. Early studies had shown that oral delivery of L. casei probiotic strains to mice could activate mononuclear phagocytes for increased phagocytic activity and lysosomal enzyme production and that this enhancement could be detected in cells derived from peritoneal exudates (Perdigon et al., 1986, 1988). Subsequent studies have confirmed that certain strains of probiotic LAB can prime peritoneal macrophage populations for enhanced phagocytosis, lysosomal enzyme production and free radical oxidant production (Perdigon et al., 1988; Gill, 1998; Matsuzaki and Chin, 2000). Further studies in murine models have reported that probiotic feeding can also enhance the activity of blood-derived phagocytes and that both mononuclear (monocyte) and polymorphonuclear (neutrophil) populations are stimulated by probiotics (Gill et al., 2000). Human studies have confirmed this effect in circulating phagocytes of adult subjects (Schiffrin et al., 1995; Donnet-Hughes et al., 1999; Yoon et al., 1999; Chiang et al., 2000; O'Mahony et al., 2000; Sheih et al., 2001) including the elderly (Arunachalam et al., 2000; Gill et al., 2001a, b, c; Table 13.1).

In common with studies on the effects on lymphocyte proliferation, it is at present unclear whether oral probiotic delivery enhances phagocytic cell function as a reflection of increased cell numbers and/or increased cellular avidity to phagocytose. It is likely that bacterial signalling will activate a general release of phagocytically active cells into circulation (Herich et al., 1999), and this is possibly achieved by microbial stimulation of phagocytic precursor cells. It is important to note that mononuclear phagocytes, in particular, are also capable of secreting immunomodulatory cytokines and that stimulation of these cells by oral probiotics has been shown to increase production of key cytokines, which modify and shape the character of the immune response (Tejada-Simon et al., 1999b). Thus, it is possible that phagocyte activation is the first and key event in immune stimulation by probiotics and that enhanced phagocytic capacity is a reliable index of this activation, prior to the initiation of downstream events, such as cytokine-mediated enhancement of leucocyte cytotoxicity and lymphocyte activation.

Studies in murine models have shown that the cytocidal activity of splenic leucocytes can also be increased following delivery of certain strains of probi-otics. Systemic priming of mice with viable L. casei (Shirota strain) can enhance ex vivo tumoricidal activity of splenic NK cells and macrophages (Kato et al., 1983, 1984) and can also increase cytocidal activity against cytomegalovirus-infected target T-cells (Ohashi et al., 1988). Oral delivery of L. rhamnosus HN001 or L. casei Shirota to mice has also been shown to increase ex vivo NK-cell tumoricidal activity (Gill et al., 2000; Matsuzaki and Chin, 2000). In human studies, feeding of L. rhamnosus (strain HN001) or Bifidobacterium lactis (strain HN019) has been demonstrated to up-regulate peripheral blood NK-cell-mediated cytotoxicity against tumour cells (Chiang et al., 2000; Gill et al., 2001a, b, c; Sheih et al., 2001; Table 13.1).

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