Cellular Renewal and Improvement of Local Cell Effector Activity in Peritoneal Cavity in Response to Infectious Stimuli

Abstract

The peritoneal cavity (PerC) is a singular compartment where many cell populations reside and interact. Despite the widely adopted experimental approach of intraperitoneal (i.p.) inoculation, little is known about the behavior of the different cell populations within the PerC. To evaluate the dynamics of peritoneal macrophage (MØ) subsets, namely small peritoneal MØ (SPM) and large peritoneal MØ (LPM), in response to infectious stimuli, C57BL/6 mice were injected i.p. with zymosan or Trypanosoma cruzi. These conditions resulted in the marked modification of the PerC myelo-monocytic compartment characterized by the disappearance of LPM and the accumulation of SPM and monocytes. In parallel, adherent cells isolated from stimulated PerC displayed reduced staining for β-galactosidase, a biomarker for senescence. Further, the adherent cells showed increased nitric oxide (NO) and higher frequency of IL-12-producing cells in response to subsequent LPS and IFN-γ stimulation. Among myelo-monocytic cells, SPM rather than LPM or monocytes, appear to be the central effectors of the activated PerC; they display higher phagocytic activity and are the main source of IL-12. Thus, our data provide a first demonstration of the consequences of the dynamics between peritoneal MØ subpopulations by showing that substitution of LPM by a robust SPM and monocytes in response to infectious stimuli greatly improves PerC effector activity.

Expression of endoglin isoforms in the myeloid lineage and their role during aging and macrophage polarization

“…Thus, it can be postulated that the increased expression of endoglin is associated with resident niches of hematopoietic stem cells or tissue macrophages. Accordingly, the resident large macrophages of the peritoneal cavity are mostly senescent (Cassado Ados et al, 2011) and show increased endoglin expression during aging (Fig. 1E).…”

“…First, macrophages were obtained from the peritoneal cavity of 2-month-old mice. Most of these cells correspond to the myeloid lineage, mainly to tissue-resident LPMs (Cassado Ados et al, 2011). As a biomarker of macrophage senescence, we used b-galactosidase activity (Cassado Ados et al, 2011).…”

“…Most of these cells correspond to the myeloid lineage, mainly to tissue-resident LPMs (Cassado Ados et al, 2011). As a biomarker of macrophage senescence, we used b-galactosidase activity (Cassado Ados et al, 2011). A large proportion of the LPMs were positive for the senescence-associated b-galactosidase staining (Fig.…”

“…During aging, immune and inflammatory responses are impaired in a general immunosenescence process where macrophage functions are compromised (Cassado Ados et al, 2011;Mahbub et al, 2012). Aged macrophages show reduced functional activity, leading to accumulation of unphagocytosed cellular debris, chronic inflammation and exacerbation of tissue damage and aging (Shaw et al, 2010;Li, 2013).…”

“…Upon inflammatory stimuli, the loss of LPMs correlates with the cell renewal of the peritoneal cavity, which is characterized by the enrichment of SPMs. All these data suggest that the peritoneal cavity is a useful tool to analyse macrophage immunosenescence in these two cell subsets (Cassado Ados et al, 2011). Macrophages participate in the immune response according to a preferential M1 or M2 polarization, which is involved not only in the response to pathogens, tumour progression and angiogenesis, but also in tissue homeostasis, autoimmunity and fibrosis (Sunderkötter et al, 1994;Werner and Alzheimer, 2006;Benoit et al, 2008).…”