In summary, we described the occurrence of IPD in a major U.S. urban center and found that incidence was associated with marked wintertime seasonality that may be partly explained by diminished exposure to UV-B radiation in winter months. Further study is needed, but this result is consistent with observed patterns of respiratory infectious disease, and would be consistent with several biologically plausible models of effect. As the nature of future changes in UV radiation related to climate change are more difficult to predict than general changes in temperatures or precipitation patterns, the implications of these findings for future pneumococcal disease epidemiology are unclear [45] . Nonetheless, we believe this obser-vation goes some way towards explaining the notable seasonality of IPD, and could conceivably lead to novel disease control strategies through improved understanding of this common and virulent infectious disease.  Listeriolysin O Is Necessary and Sufficient to Induce Autophagy during Listeria monocytogenes Infection BACKGROUND: Recent studies have suggested that autophagy is utilized by cells as a protective mechanism against Listeria monocytogenes infection. METHODOLOGY/PRINCIPAL FINDINGS: However we find autophagy has no measurable role in vacuolar escape and intracellular growth in primary cultured bone marrow derived macrophages (BMDMs) deficient for autophagy (atg5(−/−)). Nevertheless, we provide evidence that the pore forming activity of the cholesterol-dependent cytolysin listeriolysin O (LLO) can induce autophagy subsequent to infection by L. monocytogenes. Infection of BMDMs with L. monocytogenes induced microtubule-associated protein light chain 3 (LC3) lipidation, consistent with autophagy activation, whereas a mutant lacking LLO did not. Infection of BMDMs that express LC3-GFP demonstrated that wild-type L. monocytogenes was encapsulated by LC3-GFP, consistent with autophagy activation, whereas a mutant lacking LLO was not. Bacillus subtilis expressing either LLO or a related cytolysin, perfringolysin O (PFO), induced LC3 colocalization and LC3 lipidation. Further, LLO-containing liposomes also recruited LC3-GFP, indicating that LLO was sufficient to induce targeted autophagy in the absence of infection. The role of autophagy had variable effects depending on the cell type assayed. In atg5(−/−) mouse embryonic fibroblasts, L. monocytogenes had a primary vacuole escape defect. However, the bacteria escaped and grew normally in atg5(−/−) BMDMs. CONCLUSIONS/SIGNIFICANCE: We propose that membrane damage, such as that caused by LLO, triggers bacterial-targeted autophagy, although autophagy does not affect the fate of wild-type intracellular L. monocytogenes in primary BMDMs. Listeria monocytogenes is a Gram-positive, facultative intracellular, food-borne pathogen that causes severe disease in pregnant and immunocompromised hosts [1] . L. monocytogenes is also an important model organism that has been used for decades to study bacterial pathogenesis, immunology and cell biology [2] [3] [4] [5] .