Neutrophils are essential for early anti-Listeria defense in the liver, but not in the spleen or peritoneal cavity, as revealed by a granulocyte-depleting monoclonal antibody.

Abstract

SummaryThis study shows that in mice selectively depleted of neutrophils by treatment with a monoclonal antibody, RB6-8C5, listeriosis is severely exacerbated in the liver, but not in the spleen or peritoneal cavity during the crucial first day of infection. At sites of infection in the livers of neutrophildepleted mice, Listeria monocytogenes grew to large numbers inside hepatocytes. By contrast, in the livers of normal mice neutrophils rapidly accumulated at infectious loci and this was associated with the lysis of infected hepatocytes that served to abort infection in these permissive cells. In the spleen the situation was different, in that depletion of neutrophils did not result in appreciable exacerbation of infection. In this organ intact infected cells, many of which appeared to be fibroblastlike stromal cells, were found at loci of infection in the presence or absence of large numbers of neutrophils. This suggests that neutrophils are less effective at destroying L. monocytogenes-infected target cells in the spleen than in the liver. Consequently, at least during the first day, the organism remained free to multiply intracellularly in the spleen in cells that are permissive for its growth. Presumably, the same situation exists in the peritoneal cavity, because depleting neutrophils did not severely exacerbate infection initiated at this site.

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

“…3A). Consistent with previous findings [7,66,67], CFU in the liver of a-GalCeruntreated mice were significantly increased by Gr-1 1 cell depletion (Fig. 3B).…”

“…After L. monocytogenes infection, numbers of CD11b 1 Gr-1 1 cells in the liver of mice treated with a-GalCer were markedly lower than those of mice left untreated or treated with vehicle. Since (i) a-GalCer treatment numerically increased liver CD11b 1 Gr-1 1 cells and (ii) CD11b 1 Gr-1 1 cells, in particular neutrophils, play a central role as a first line of defense against L. monocytogenes infection [6][7][8], we consider it likely that most of bacteria residing in the liver were eliminated by CD11b 1 Gr-1 1 cells stimulated by a-GalCer treatment prior to infection. Under pathologic conditions, Gr-1 1 cells may injure normal tissue by releasing reactive oxygen intermediates, toxic cationic proteins, and degradative enzymes [77].…”

“…We therefore determined whether amelioration of listeriosis by a-GalCer treatment was caused by accelerated infiltration of inflammatory cells into the liver. Because Gr-1 1 cells serve as a first line of defense against L. monocytogenes infection, in particular in the liver [6][7][8]66, 67], we compared numbers of Gr-1 1 cells in the liver before and after a-GalCer treatment. Because CD11b surface expression is up-regulated on Gr-1 1 cells after activation [68], CD11b expression was analyzed, as well.…”

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

“…In immunocompetent mice, intravenous injection of a small number of L. monocytogenes causes an acute infection of spleen and liver that is cleared within 7 to 8 days [2,3]. Neutrophils and monocytes are rapidly recruited to sites of bacterial infection and are required for initial control of L. monocytogenes infection [4,5]. Interestingly, in the infected spleen, live L. monocytogenes are mostly found in T cell zones of the white pulp [6].…”

Indoleamine 2,3-dioxygenase–expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection

“…Using markers specific for B cells (CD20) and T cells (CD3), we demonstrated that these specialized cells of the adaptive immune response are not part of granulomas in listeriosis but are almost exclusively located in between granulomas. Since macrophages and neutrophils are known to play major roles in systemic listeriosis in murine models (8,25,26), we next assessed expression of CD15 (granulocyte marker) (27) and CD68 (macrophage marker) (28) in infected tissues ( Figure 1A). Within the center of the granulomas, basically all cells were CD15 + granulocytes, with only a few CD68 + macrophages.…”