TNF Drives Monocyte Dysfunction with Age and Results in Impaired Anti-pneumococcal Immunity

• DOI: 10.1371/journal.ppat.1005368
• Publication Date: 2016-01-15T02:09:43Z
• Authors: Alicja Puchta; Avee Naidoo; Chris P. Verschoor; Dessi Loukov; Netusha Thevaranjan; Talveer S. Mandur; Phuong-son Nguyen; Manel Jordana; Mark Loeb; Zhou Xing; Lester Kobzik; Maggie J. Larché; Dawn M. E. Bowdish
• Keywords: Monocyte; CCR2; CD16

Monocyte phenotype and output changes with age, but why this occurs how it impacts anti-bacterial immunity are not clear. We found that, in both humans mice, circulating monocyte function was altered age due to increasing levels of TNF the circulation that occur as part aging process. Ly6C+ monocytes from old (18-22 mo) mice CD14+CD16+ intermediate/inflammatory older adults also contributed "age-associated inflammation" they produced more inflammatory cytokines IL6 steady state when stimulated bacterial products. Using an aged mouse model pneumococcal colonization we chronic exposure maturity monocytes, measured by F4/80 expression, decrease maturation directly linked susceptibility infection. had higher CCR2 which promoted premature egress bone marrow challenged Streptococcus pneumoniae. Although recruitment blood nasopharnyx were during S. pneumoniae colonization, clearance impaired. Counterintuitively, elevated excessive impaired anti-pneumococcal since improved upon pharmacological reduction or major producers TNF. Thus, impairs development, promotes egress, contribute systemic inflammation is ultimately detrimental immunity.