Probiotic Lactobacillus strains protect against myelosuppression and immunosuppression in cyclophosphamide-treated mice.

This work evaluated the capacity of two probiotic strains, Lactobacillus casei CRL431 and Lactobacillus rhamnosus CRL1506, to protect against myelosuppression and immunosuppression in cyclophosphamide (Cy)-treated mice. Changes in mature granulocytes and progenitor cells in bone marrow (BM) and blood were studied. In addition, the ability of probiotics to accelerate the recovery of the immune response against the opportunistic pathogen Candida albicans was evaluated. We demonstrated for the first time that the preventive treatment with immunomodulatory lactobacilli such as L. casei CRL431 or L. rhamnosus CRL1506 was able to increase immature myeloid progenitors in the BM, allowing an early recovery of myeloid cells after Cy administration. Probiotic lactobacilli were also capable to induce an early recovery of neutrophils in blood, improve phagocytic cells recruitment to infectious sites and increase the resistance against the opportunistic pathogen C. albicans. Although deeper studies regarding the cellular and molecular mechanisms of probiotic actions are needed, these findings support the idea that strains like CRL431 and CRL1506 may accelerate the recovery of Cy-caused immunosuppression by immunopotentiating myeloid cells. Then, probiotic lactobacilli have the potential to be used as alternatives for lessening chemotherapy-induced immunosuppression in cancer patients.

Effect of mycoplasmas on apoptosis of 32D cells is species-dependent.

We previously showed that mycoplasmal infection effectively prevented apoptosis of infected cells, whereas other researchers have indicated that mycoplasmal infection promoted apoptosis. To understand the mechanism underlying this discrepancy, five different species of mycoplasmas were investigated for their effects on apoptosis of interleukin (IL)-3-dependent 32D cells. Results revealed that Mycoplasma fermentans and M. penetrans effectively supported continuous growth of 32D cells after IL-3 withdrawal. M. fermentans was more potent than M. penetrans. This effect was achieved by way of preventing apoptosis and stimulating cell proliferation. On the contrary, M. hominis and M. salivarium accelerated apoptosis of 32D cells. M. genitalium had no significant effect on apoptosis. The RNase protection assay indicated that the proapoptotic and antiapoptotic mycoplasmas altered the expression of major apoptosis regulatory genes differently. The difference in apoptosis regulatory gene expression induced by different species of mycoplasmas might be accountable for their effects on host cell apoptosis.

Cytomegalovirus MCK-2 controls mobilization and recruitment of myeloid progenitor cells to facilitate dissemination.

Murine cytomegalovirus encodes a secreted, pro-inflammatory chemokine-like protein, MCK-2, that recruits leukocytes and facilitates viral dissemination. We have shown that MCK-2-enhanced recruitment of myelomonocytic leukocytes with an immature phenotype occurs early during infection and is associated with efficient viral dissemination. Expression of MCK-2 drives the mobilization of a population of leukocytes from bone marrow that express myeloid marker Mac-1 (CD11b), intermediate levels of Gr-1 (Ly6 G/C), platelet-endothelial-cell adhesion molecule-1 (PECAM-1, CD31), together with heterogeneous levels of stem-cell antigen-1 (Sca-1, Ly-6 A /E). Recombinant MCK-2 mediates recruitment of this population even in the absence of viral infection. Recruitment of this cell population and viral dissemination via the bloodstream to salivary glands proceeds normally in mice that lack CCR2 and MCP-1 (CCL2), suggesting that recruitment of macrophages is not a requisite component of pathogenesis. Thus, a systemic impact of MCK-2 enhances the normal host response and causes a marked increase in myelomonocytic recruitment with an immature phenotype to initial sites of infection. Mobilization influences levels of virus dissemination via the bloodstream to salivary glands and is dependent on a myelomonocytic cell type other than mature macrophages.