Cytokines Influencing Infections by Rickettsia Species

Turco, Jenifer; Winkler, Herbert H.

doi:10.1007/0-306-46804-2_3

Cited by 3 publications

(2 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, cytokine-treated human macrophages restrict the growth of R. prowazekii (38); however, evidence that human macrophages produce large amounts of NO is lacking. Second, R. prowazekii strains resistant to cytokine-induced, NOS-independent inhibition of their growth in mouse L929 cells are also resistant to IFN-␥-induced inhibition of their growth in human fibroblasts (30). The possible role of the NOS pathway in altering interactions between R. prowazekii organisms and human host cells has not been adequately evaluated, and (to our knowledge) cytokine-induced suppression of the initial R. prowazekii infection in human cells has not been reported.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, such investigations determined that a lack of the amino acid tryptophan does not explain the ability of IFN-␥ to limit the growth of R. prowazekii in either mouse L929 cells (in which tryptophan is not depleted in response to IFN-␥) or human fibroblasts (in which reconstitution of the depleted tryptophan pool in IFN-␥-treated cells does not alleviate the inhibition of rickettsial growth) (25). Furthermore, such studies revealed (i) that both NOS-independent and NOS-dependent mechanisms are involved in suppressing the growth of R. prowazekii in mouse L929 cells treated with IFN-␥ plus TNF-␣ (28), (ii) that the inhibition of growth of R. prowazekii observed in L929 cells treated with either IFN-␥ alone or TNF-␣ alone is largely NOS independent (28), (iii) that the mechanism responsible for IFN-␥-induced, NOS-independent inhibition of growth of R. prowazekii in mouse L929 cells is likely to exist also in IFN-␥-treated human fibroblasts (30), and (iv) that the cytotoxic effects on host cells brought about by the combination of cytokine treatment and R. prowazekii infection are not dependent on NOS (28,29). These effects of cytokine treatment on R. prowazekii-host cell interactions are observed in host cells infected with either the virulent Breinl strain or the avirulent Madrid E strain of R. prowazekii.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Nitric Oxide-Mediated Inhibition of the Ability ofRickettsia prowazekiiTo Infect Mouse Fibroblasts and Mouse Macrophagelike Cells

et al. 1998

Self Cite

View full text Add to dashboard Cite

The role of the nitric oxide synthase (NOS) pathway in inhibiting the ability of Rickettsia prowazekii to initially infect (invade) mouse cytokine-treated, fibroblastic L929 cells and macrophagelike RAW264.7 cells and the ability of nitric oxide (NO) to damage isolated rickettsiae were investigated. Substantial amounts of nitrite (a degradation product of NO) were produced and the initial rickettsial infection was suppressed in cultures of L929 cells treated with crude lymphokine preparations (LK) or with gamma interferon (IFN-γ) plus tumor necrosis factor alpha (TNF-α) but not in L929 cell cultures treated with IFN-γ alone or TNF-α alone. The NOS inhibitors N G-methyl-l-arginine and aminoguanidine both inhibited nitrite production and prevented the suppression of the initial rickettsial infection. Antibody-mediated neutralization of the IFN-γ in the LK also inhibited both nitrite production and suppression of the initial rickettsial infection. Cultures of RAW264.7 cells treated with IFN-γ plus lipopolysaccharide exhibited suppression of the initial rickettsial infection, and the suppression was relieved by aminoguanidine. Addition of oxyhemoglobin (a scavenger of extracellular NO) during the rickettsial infection alleviated the suppression of the initial rickettsial infection observed in appropriately treated L929 cells and RAW264.7 cells. In addition, the oxyhemoglobin restored the rickettsia-mediated, rapid killing of the treated RAW264.7 cells. Incubation of isolated rickettsiae with NO inhibited their ability to infect L929 and IFN-γ-treated RAW264.7 cells and to rapidly kill IFN-γ-treated RAW264.7 cells. In contrast, incubation of L929 cells with a solution that contained NO and/or degradation products of NO did not affect their ability to be infected by rickettsiae. The data are consistent with the hypothesis that NO released from appropriately stimulated potential host cells kills extracellular rickettsiae and thus prevents the rickettsiae from infecting the cells.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%