Overall, we show that blockade of early type I IFN signaling increases the ratio of CD4+ T cells to neutrophils in TB lesions of both C57BL/6 and C3HeB/FeJ mice, suggesting that early induction of type I IFN signaling during M. tuberculosis infection acts to favor neutrophil accumulation and limit CD4+ T cell infiltration into developing granulomatous lesions, with the timing and magnitude of this common mechanism differing on susceptible and resistant backgrounds. The gene discussed is CD4; the disease is tuberculosis.