Bacterial infections sometimes occur as superinfection following viral infec­tions. In this situation, macrophages usually represent the rst line of defense. These macrophages are also responsible for recruiting and activating other immune cells and controlling the spread of bacterial infections. Inammatory response to extra­cellular bacteria, such as S. pneumoniae, is primarily driven by neutrophil inltra­tion and secondarily by a late adaptive immunity regulated by Th1 and Th17 cells. Additionally, the production of specic antibodies against the microorganisms is provided by B lymphocytes [27]. Of note, IgM, IgG, and IgA are fundamental in the response against bacteria, and particularly capsulated bacteria, as shown by the recurrence of S. pneumoniae and H. inuenzae infections in patients with primary antibody deciencies (PAD), often leading to airway remodeling and bronchiectasis [30]. Notably, the evaluation of the antibody response to vaccination is part of the diagnostic process of common variable immunodeciency. In these patients with a suspicion of PAD, the assessment of the response to pneumococcal polysaccharide vaccines is used as a gold standard to assess T-independent antibody responses [31]. In particular, between IgG subclasses, IgG2 plays a prominent role as an anti­polysaccharide antibody. Also, specic antibody deciencies are reported, in which a specic inability to mount an antibody response against puried Streptococcus pneumoniae capsular polysaccharide antigens is detected. This may occur despite normal total IgG, IgA, and IgM levels and preserved antibody responses to protein antigens [32].