Effect of cytokine interplay on macrophage polarization during chronic XXXX with @entity1327 .

@entity32 @entity19 @entity1327 @entity281 @entity364 @entity358 @entity842 @entity164 @entity58 @entity20585
The immune response to @entity1327 following @entity358 of C57BL/6 @entity164 ( @entity164 ) @entity19 results in the development of @entity281 with characteristics of @entity20585 ( @entity20585 ). To further clarify the role of Th1/Th2 polarizing cytokines in this model, we performed kinetic analysis of cytokine responses and compared cytokine profiles, pathologies, and macrophage (Mac) polarization status in @entity1327 -infected @entity164 , interleukin-4-deficient ( @entity58 (-/-)), and gamma interferon-deficient (IFN-y(-/-)) C57BL/6 @entity19 . Results show that cytokine expression in the infected @entity164 @entity19 is not permanently Th2 biased but changes dynamically over time. Using multiple Mac activation markers, we further demonstrate that @entity58 and IFN-y regulate the polarization state of Macs in this model. A higher @entity58 /IFN-y ratio leads to the development of alternatively activated Macs (aaMacs), whereas a higher IFN-y/ @entity58 ratio leads to the generation of classically activated Macs (caMacs). @entity164 @entity19 that coexpress @entity58 and IFN-y during @entity364 concurrently display both types of Mac polarization markers. Concurrent stimulation of Macs with IFN-y and @entity58 results in an upregulation of both sets of markers within the same cells, i.e., formation of an intermediate aaMac/caMac phenotype. These cells express both inducible @entity842 synthase (important for clearance) and arginase (associated with chronic/progressive @entity281 ). Together, our data demonstrate that the interplay between Th1 and Th2 cytokines supports @entity281 , @entity32 , and the development of @entity20585 pathology in @entity1327 -infected lungs. This cytokine interplay modulates Mac differentiation, including generation of an intermediate caMac/aaMac phenotype, which in turn may support chronic "steady-state" @entity364 and the resultant @entity20585 pathology.
