Macrophage Nitric Oxide Mediates Immunosuppression in Infectious Inflammation

Eisenstein, Toby K.; Huang, Duan; Meissler, Joseph J.; al-Ramadi, Basel K.

doi:10.1016/s0171-2985(11)80455-9

Cited by 80 publications

(54 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Infection with aroA mutant or wildtype Salmonella results in a profound state of generalized immune suppression (2)(3)(4)14) attributed to the effects of NO produced by myeloid-derived suppressor cells that curtail the induction of adaptive immunity (13). In contrast, a state of immune suppression is not observed in dam mutant-immunized animals (26).…”

Section: Resultsmentioning

confidence: 99%

“…Such generalized immune suppression may also limit vaccination efficiency and increase susceptibility to infectious disease. For example, infection with live attenuated vaccines (i.e., aroA mutant) or wild-type Salmonella results in a transient state of generalized immune suppression (2)(3)(4)14) attributed to the effects of nitric oxide (NO) produced by MDSCs. The aroA-associated immune suppression may restrict the nature of adaptive immunity induced, limiting protective efficiency to only closely related strains (25,30,31).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Conditions That Diminish Myeloid-Derived Suppressor Cell Activities Stimulate Cross-Protective Immunity

et al. 2008

View full text Add to dashboard Cite

Immunity conferred by conventional vaccines is restricted to a narrow range of closely related strains, highlighting the unmet medical need for the development of vaccines that elicit protection against multiple pathogenic serotypes. Here we show that a Salmonella bivalent vaccine comprised of strains that lack and overproduce DNA adenine methylase (Dam) conferred cross-protective immunity to salmonella clinical isolates of human and animal origin. Protective immunity directly correlated with increased levels of cross-reactive opsonizing antibodies and memory T cells and a diminished expansion of myeloid-derived suppressor cells (MDSCs) that are responsible for the immune suppression linked to several conditions of host stress, including chronic microbial infections, traumatic insults, and many forms of cancer. Further, aged mice contained increased numbers of MDSCs and were more susceptible to Salmonella infection than young mice, suggesting a role for these cells in the immune declines associated with the natural aging process. These data suggest that interventions capable of reducing MDSC presence and activities may allow corresponding increases in B-and T-cell stimulation and benefit the ability of immunologically diverse populations to be effectively vaccinated as well as reducing the risk of susceptible individuals to infectious disease.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Conditions That Diminish Myeloid-Derived Suppressor Cell Activities Stimulate Cross-Protective Immunity

et al. 2008

View full text Add to dashboard Cite

show abstract

“…It transpires that suppression of antibody responses is mediated by iNOS within Mws. [39][40][41][42] Collectively, we argue that, in addition to bridging the gap between innate and adaptive immunity, resolution may also establish a phase of immunologic tolerance. It is unclear why a PMN-driven, acute onset phase of inflammation should be accompanied, paradoxically, by a prolonged phase of immune suppression.…”

Section: Discussionmentioning

confidence: 99%

Resolution of acute inflammation bridges the gap between innate and adaptive immunity

Newson

Stables

Karra

et al. 2014

Blood

145

163

View full text Add to dashboard Cite

show abstract

“…However, it is important to note that • NO induces immunosuppression by impairing T cell function. Early works have suggested its participation in the immunosuppression developed during infectious diseases characterized by strong macrophage activation, including T. brucei (34) and Salmonella typhimurium (35). During T. cruzi infection, it has been shown that the inhibition of the proliferative response of T lymphocytes of infected mice could be restored by the addition of L-NMMA (30).…”

Section: Discussionmentioning

confidence: 99%

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Naviliat

Gualco

Cayota

et al. 2005

Braz J Med Biol Res

View full text Add to dashboard Cite

Tyrosine nitration is a post-translational modification resulting from the addition of a nitro (-NO 2 ) group to the ortho-position of tyrosine residues. Detection of protein 3-nitrotyrosine is regarded as a marker of nitro-oxidative stress and is observed in inflammatory processes. The formation and role of nitrating species in the control and myocardiopathy of T. cruzi infection remain to be studied. We investigated the levels of • NO and protein 3-nitrotyrosine in the plasma of C3H and BALB/c mice and pharmacologically modulated their production during the acute phase of T. cruzi infection. We also looked for protein 3-nitrotyrosine in the hearts of infected animals. Our results demonstrated that C3H animals produced higher amounts of • NO than BALB/c mice, but their generation of peroxynitrite was not proportionally enhanced and they had higher parasitemias. While N G -nitroarginine methyl ester treatment abolished • NO production and drastically augmented the parasitism, mercaptoethylguanidine and guanidoethyl disulfide, at doses that moderately reduced the • NO and 3-nitrotyrosine levels, paradoxically diminished the parasitemia in both strains. Nitrated proteins were also demonstrated in myocardial cells of infected mice. These data suggest that the control of T. cruzi infection depends not only on the capacity to produce • NO, but also on its metabolic fate, including the generation of nitrating species that may constitute an important element in parasite resistance and collateral myocardial damage.

show abstract

Macrophage Nitric Oxide Mediates Immunosuppression in Infectious Inflammation

Cited by 80 publications

References 14 publications

Conditions That Diminish Myeloid-Derived Suppressor Cell Activities Stimulate Cross-Protective Immunity

Conditions That Diminish Myeloid-Derived Suppressor Cell Activities Stimulate Cross-Protective Immunity

Resolution of acute inflammation bridges the gap between innate and adaptive immunity

Protein 3-nitrotyrosine formation during Trypanosoma cruzi infection in mice

Contact Info

Product

Resources

About