Arginase-1 Is Responsible for IL-13-Mediated Susceptibility to Infection.

Arginase-1 (Arg-1) is a marker for alternatively activated macrophages (AAM) and is mainly induced by the type 2 cytokines interleukin (IL)-4 and IL-13 through the common IL-4 receptor-alpha (Rα) subunit. Both, Arg-1 and AAM undermine macrophage effector functions against intracellular parasites and are therefore implicated in the susceptibility to infection with , the causative agent of Chagas' disease. However, the involvement of Arg-1 in promoting intracellular replication of in AAM has not been proven so far .

Suppressor of Cytokine Signaling 3 in Macrophages Prevents Exacerbated Interleukin-6-Dependent Arginase-1 Activity and Early Permissiveness to Experimental Tuberculosis.

Suppressor of cytokine signaling 3 (SOCS3) is a feedback inhibitor of interleukin (IL)-6 signaling in macrophages. In the absence of this molecule, macrophages become extremely prone to an IL-6-dependent expression of arginase-1 (Arg1) and nitric oxide synthase (NOS)2, the prototype markers for alternative or classical macrophage activation, respectively. Because both enzymes are antipodean macrophage effector molecules in () infection, we assessed the relevance of SOCS3 for macrophage activation during experimental tuberculosis using macrophage-specific SOCS3-deficient (LysMSOCS3) mice.

The IL-13/IL-4Rα axis is involved in tuberculosis-associated pathology.

Human tuberculosis (TB) is a leading global health threat and still constitutes a major medical challenge. However, mechanisms governing tissue pathology during post-primary TB remain elusive, partly because genetically or immunologically tractable animal models are lacking. In human TB, the demonstration of a large relative increase in interleukin (IL)-4 and IL-13 expression, which correlates with lung damage, indicates that a subversive T helper (TH)2 component in the response to Mycobacterium tuberculosis (Mtb) may undermine protective immunity and contribute to reactivation and tissue pathology.

9- and 11-Substituted 4-azapaullones are potent and selective inhibitors of African trypanosoma.

Trypanosomes from the "brucei" complex are pathogenic parasites endemic in sub-Saharan Africa and causative agents of severe diseases in humans and livestock. In order to identify new antitrypanosomal chemotypes against African trypanosomes, 4-azapaullones carrying α,β-unsaturated carbonyl chains in 9- or 11-position were synthesized employing a procedure with a Heck reaction as key step. Among the so prepared compounds, 5a and 5e proved to be potent antiparasitic agents with antitrypanosomal activity in the submicromolar range.