Complement is an important innate immune defense system that deploys efficient immunosurveillance and protection against pathogens and damaged host cells, and plays crucial roles in inflammation (1). The complement comprises over 50 effectors and receptors, which precisely balance activation, amplification and regulation of the complement proteolytic cascade organized by three canonical pathways (2). However, the complement often becomes host-offensive and leads to pathophysiological situations once disordered (3).Pentraxins are a superfamily of conserved multi-functional pattern recognition molecules (PRMs) with features of a cyclic multimeric structure and a conserved C-terminal pentraxin domain. As major members of the pentraxin family, C-reactive protein (CRP), serum-amyloid P component (SAP) and pentraxin 3 (PTX3) are synthesized mainly in response to inflammatory mediators and tissue injury, and function as essential constituents in innate immune defense against certain pathogenic intruders (4). Featuring antibody-like common properties, CRP, SAP and PTX3 often induce rapid and efficient immune effector mechanisms upon selective recognition of microbial moieties (5). Interestingly, recent data have shown that interaction between pentraxins and complement could build up comprehensive crosstalk with the three pathways of complement cascade activation (6).This Research Topic aims at collecting the latest findings to gain deeper insight into the functional roles of pentraxins in infection and regulation of inflammatory responses with a focus on the interaction with the complement system, thus directing potential therapeutic applications.Both pentraxins and complement play a non-redundant role in resistance to invasive pulmonary aspergillosis caused by Aspergillus fumigatus (A. fumigatus), but their crosstalk also has a synergic effect on their immune effector functions. Dellière et al. dissect the regulation of alveolar humoral immune components during A. fumigatus infection (7). Using comparative proteomic analysis of the bronchoalveolar lavage (BAL) fluid collected from individuals infected or colonized with A. fumigatus, they identified several humoral immune components affected by A. fumigatus infection and colonization. In agreement with previous findings, both complement factors and pentraxins were found as the major humoral immune components, for instance C1q, ficolin-2, MASP-2 and PTX3. These findings further substantiate an essential contribution of these PRMs and their synergistic effects via crosstalk during A. fumigatus-caused infection and inflammation. Further, the