A 38-year-old man comes to the office due to worsening fever, chills, malaise, cough, and shortness of breath. The patient has no prior medical conditions and does not use tobacco, alcohol, or illicit drugs. He has not traveled recently or been exposed to sick contacts. Temperature is 39.4 C (103 F). There is dullness to percussion and crackles over the right lung. Leukocyte count is elevated, and chest x-ray reveals a right lung infiltrate. The underlying immune response to this patient's infection largely involves T helper (Th1) cells, interferon-gamma, and interleukin-2. Which of the following is the most likely pathogen responsible for this patient's pneumonia?
This patient has high fever, cough, leukocytosis, and a right lung infiltrate indicating lobar pneumonia. Lobar pneumonia is most commonly caused by extracellular bacterial pathogens such as Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pneumoniae (Choices A, D, and E). The immune response to extracellular organisms is primarily mediated by neutrophils early in infection and by the humoral antibody response (B lymphocytes, immunoglobulins, complement) as time goes on.
In this case, components of the cell-mediated immune response were primarily involved in controlling the infection, suggesting that the pneumonia was most likely due to an intracellular pathogen such as Legionella pneumophila (a common cause of atypical community-acquired pneumonia). Intracellular pathogens are phagocytosed by macrophages but are initially resistant to destruction due to the presence of virulence factors that inhibit phagosome-lysosome fusion (eg, Legionella) or phagolysosome acidification (eg, Mycobacteria tuberculosis), or allow bacteria to escape from the phagolysosome (eg, Listeria monocytogenes).
Legionella and other intracellular pathogens that initially replicate within the phagosome eventually undergo some degree of digestion by lysosomes, leading to the display of bacterial antigens on major histocompatibility complex (MHC) class II molecules. This stimulates naïve CD4 T lymphocytes to differentiate into T-helper subtype 1 (Th1) cells. Th1 cells release interferon-gamma, which activates macrophages and allows them to form fully mature (acidified) phagolysosomes capable of efficiently killing the intracellular bacteria. Th1 cells also release interleukin-2, which activates and expands the population of naïve T cells, Th1 cells, and memory T cells.
(Choice C) Pseudomonas aeruginosa is a common cause of pneumonia in patients who are hospitalized in the intensive care unit or those with structural lung disease such as chronic obstructive pulmonary disease. It is an extracellular pathogen primarily combated by neutrophils and the humoral immune response.
Educational objective:
Intracellular bacterial organisms such as Legionella pneumophila are primarily countered by the cell-mediated immune response. Intracellular pathogens that replicate within phagosomes (eg, Legionella, Mycobacterium tuberculosis) trigger activation and differentiation of T-helper subtype 1 cells with subsequent macrophage activation via interferon-gamma.